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1
Cibulsky, Susan M., and William A. Sather. "The Eeee Locus Is the Sole High-Affinity Ca2+ Binding Structure in the Pore of a Voltage-Gated Ca2+ Channel." Journal of General Physiology 116, no. 3 (August 14, 2000): 349–62. http://dx.doi.org/10.1085/jgp.116.3.349.
Повний текст джерелаАнотація:
Selective permeability in voltage-gated Ca2+ channels is dependent upon a quartet of pore-localized glutamate residues (EEEE locus). The EEEE locus is widely believed to comprise the sole high-affinity Ca2+ binding site in the pore, which represents an overturning of earlier models that had postulated two high-affinity Ca2+ binding sites. The current view is based on site-directed mutagenesis work in which Ca2+ binding affinity was attenuated by single and double substitutions in the EEEE locus, and eliminated by quadruple alanine (AAAA), glutamine (QQQQ), or aspartate (DDDD) substitutions. However, interpretation of the mutagenesis work can be criticized on the grounds that EEEE locus mutations may have additionally disrupted the integrity of a second, non-EEEE locus high-affinity site, and that such a second site may have remained undetected because the mutated pore was probed only from the extracellular pore entrance. Here, we describe the results of experiments designed to test the strength of these criticisms of the single high-affinity locus model of selective permeability in Ca2+ channels. First, substituted-cysteine accessibility experiments indicate that pore structure in the vicinity of the EEEE locus is not extensively disrupted as a consequence of the quadruple AAAA mutations, suggesting in turn that the quadruple mutations do not distort pore structure to such an extent that a second high affinity site would likely be destroyed. Second, the postulated second high-affinity site was not detected by probing from the intracellularly oriented pore entrance of AAAA and QQQQ mutants. Using inside-out patches, we found that, whereas micromolar Ca2+ produced substantial block of outward Li+ current in wild-type channels, internal Ca2+ concentrations up to 1 mM did not produce detectable block of outward Li+ current in the AAAA or QQQQ mutants. These results indicate that the EEEE locus is indeed the sole high-affinity Ca2+ binding locus in the pore of voltage-gated Ca2+ channels.
2
Cloues, Robin K., Susan M. Cibulsky, and William A. Sather. "Ion Interactions in the High-Affinity Binding Locus of a Voltage-Gated Ca2+ Channel." Journal of General Physiology 116, no. 4 (September 25, 2000): 569–86. http://dx.doi.org/10.1085/jgp.116.4.569.
Повний текст джерелаАнотація:
The selectivity filter of voltage-gated Ca2+ channels is in part composed of four Glu residues, termed the EEEE locus. Ion selectivity in Ca2+ channels is based on interactions between permeant ions and the EEEE locus: in a mixture of ions, all of which can pass through the pore when present alone, those ions that bind weakly are impermeant, those that bind more strongly are permeant, and those that bind more strongly yet act as pore blockers as a consequence of their low rate of unbinding from the EEEE locus. Thus, competition among ion species is a determining feature of selectivity filter function in Ca2+ channels. Previous work has shown that Asp and Ala substitutions in the EEEE locus reduce ion selectivity by weakening ion binding affinity. Here we describe for wild-type and EEEE locus mutants an analysis at the single channel level of competition between Cd2+, which binds very tightly within the EEEE locus, and Ba2+ or Li+, which bind less tightly and hence exhibit high flux rates: Cd2+ binds to the EEEE locus ∼104× more tightly than does Ba2+, and ∼108× more tightly than does Li+. For wild-type channels, Cd2+ entry into the EEEE locus was 400× faster when Li+ rather than Ba2+ was the current carrier, reflecting the large difference between Ba2+ and Li+ in affinity for the EEEE locus. For the substitution mutants, analysis of Cd2+ block kinetics shows that their weakened ion binding affinity can result from either a reduction in blocker on rate or an enhancement of blocker off rate. Which of these rate effects underlay weakened binding was not specified by the nature of the mutation (Asp vs. Ala), but was instead determined by the valence and affinity of the current-carrying ion (Ba2+ vs. Li+). The dependence of Cd2+ block kinetics upon properties of the current-carrying ion can be understood by considering the number of EEEE locus oxygen atoms available to interact with the different ion pairs.
3
Huang, Chien-Jung, Isabelle Favre, and Edward Moczydlowski. "Permeation of Large Tetra-Alkylammonium Cations through Mutant and Wild-Type Voltage-Gated Sodium Channels as Revealed by Relief of Block at High Voltage." Journal of General Physiology 115, no. 4 (April 1, 2000): 435–54. http://dx.doi.org/10.1085/jgp.115.4.435.
Повний текст джерелаАнотація:
Many large organic cations are potent blockers of K+ channels and other cation-selective channels belonging to the P-region superfamily. However, the mechanism by which large hydrophobic cations enter and exit the narrow pores of these proteins is obscure. Previous work has shown that a conserved Lys residue in the DEKA locus of voltage-gated Na+ channels is an important determinant of Na+/K+ discrimination, exclusion of Ca2+, and molecular sieving of organic cations. In this study, we sought to determine whether the Lys(III) residue of the DEKA locus interacts with internal tetra-alkylammonium cations (TAA+) that block Na+ channels in a voltage-dependent fashion. We investigated block by a series of TAA+ cations of the wild-type rat muscle Na+ channel (DEKA) and two different mutants of the DEKA locus, DEAA and DERA, using whole-cell recording. TEA+ and larger TAA+ cations block both wild-type and DEAA channels. However, DEAA exhibits dramatic relief of block by large TAA+ cations as revealed by a positive inflection in the macroscopic I–V curve at voltages greater than +140 mV. Paradoxically, relief of block at high positive voltage is observed for large (e.g., tetrapentylammonium) but not small (e.g., TEA+) symmetrical TAA+ cations. The DEKA wild-type channel and the DERA mutant exhibit a similar relief-of-block phenomenon superimposed on background current rectification. The results indicate: (a) hydrophobic TAA+ cations with a molecular diameter as large as 15 Å can permeate Na+ channels from inside to outside when driven by high positive voltage, and (b) the Lys(III) residue of the DEKA locus is an important determinant of inward rectification and internal block in Na+ channels. From these observations, we suggest that hydrophobic interfaces between subunits, pseudosubunits, or packed helices of P-region channel proteins may function in facilitating blocker access to the pore, and may thus play an important role in the blocking and permeation behavior of large TAA+ cations and potentially other kinds of local anesthetic molecules.
4
Puil, E., B. Gimbarzevsky, and R. M. Miura. "Quantification of membrane properties of trigeminal root ganglion neurons in guinea pigs." Journal of Neurophysiology 55, no. 5 (May 1, 1986): 995–1016. http://dx.doi.org/10.1152/jn.1986.55.5.995.
Повний текст джерелаАнотація:
Passive and active (voltage- and time-dependent) membrane properties of trigeminal root ganglion neurons of decerebrate guinea pigs have been determined using frequency-domain analyses of small-amplitude perturbations of membrane voltage. The complex impedance functions of trigeminal ganglion neurons were computed from the ratios of the fast Fourier transforms of the intracellularly recorded voltage response from the neuron and of the input current, which had a defined oscillatory waveform. The impedance magnitude functions and corresponding impedance locus diagrams were fitted with various membrane models such that the passive and active properties were quantified. The complex impedances of less than one-quarter of the 105 neurons which were investigated extensively could be described by the complex impedance function for a simple RC-electrical circuit. In such neurons, the voltage responses to constant-current pulses, using conventional bridge-balance techniques, could be fitted with single exponential curves, also suggesting passive membrane behavior. A nonlinear least-squares fit of the complex impedance function for the simple model to the experimentally observed complex impedance yielded estimates of the resistance of the electrode, and of input capacitance (range, 56 to 490 pF) and input resistance (range, 0.8 to 30 M omega) of the neurons. The majority of trigeminal ganglion neurons were characterized by a resonance in the 50- to 250-Hz bandwidth of their impedance magnitude functions. Such neurons when injected with "large" hyperpolarizing current pulses using bridge-balance techniques showed membrane voltage responses that "sagged" (time-dependent rectification). Also, repetitive firing commonly occurred with depolarizing current pulses; this characteristic of neurons with resonance in their impedance magnitude functions was not observed in neurons with "purely" passive membrane behavior. A nonlinear least-squares fit of a five-parameter impedance fitting function based on a membrane model to the impedance locus diagram of a neuron with resonance yielded estimates of its membrane properties: input capacitance, the time-invariant part of the conductance, the conductance activated by the small oscillatory input current, and the relaxation time constant for this conductance. The ranges of the estimates for input capacitance and input resistance were comparable to the ranges of corresponding properties derived for neurons exhibiting "purely" passive behavior.(ABSTRACT TRUNCATED AT 400 WORDS)
5
Sun, Ye-Ming, Isabelle Favre, Laurent Schild, and Edward Moczydlowski. "On the Structural Basis for Size-selective Permeation of Organic Cations through the Voltage-gated Sodium Channel." Journal of General Physiology 110, no. 6 (December 1, 1997): 693–715. http://dx.doi.org/10.1085/jgp.110.6.693.
Повний текст джерелаАнотація:
Recent evidence indicates that ionic selectivity in voltage-gated Na+ channels is mediated by a small number of residues in P-region segments that link transmembrane elements S5 and S6 in each of four homologous domains denoted I, II, III, and IV. Important determinants for this function appear to be a set of conserved charged residues in the first three homologous domains, Asp(I), Glu(II), and Lys(III), located in a region of the pore called the DEKA locus. In this study, we examined several Ala-substitution mutations of these residues for alterations in ionic selectivity, inhibition of macroscopic current by external Ca2+ and H+, and molecular sieving behavior using a series of organic cations ranging in size from ammonium to tetraethylammonium. Whole-cell recording of wild-type and mutant channels of the rat muscle μ1 Na+ channel stably expressed in HEK293 cells was used to compare macroscopic current–voltage behavior in the presence of various external cations and an intracellular reference solution containing Cs+ and very low Ca2+. In particular, we tested the hypothesis that the Lys residue in domain III of the DEKA locus is responsible for restricting the permeation of large organic cations. Mutation of Lys(III) to Ala largely eliminated selectivity among the group IA monovalent alkali cations (Li+, Na+, K+, Rb+, Cs+) and permitted inward current of group IIA divalent cations (Mg2+, Ca2+, Sr2+, Ba2+). This same mutation also resulted in the acquisition of permeability to many large organic cations such as methylammonium, tetramethylammonium, and tetraethylammonium, all of which are impermeant in the native channel. The results lead to the conclusion that charged residues of the DEKA locus play an important role in molecular sieving behavior of the Na+ channel pore, a function that has been previously attributed to a hypothetical region of the channel called the “selectivity filter.” A detailed examination of individual contributions of the Asp(I), Glu(II), and Lys(III) residues and the dependence on molecular size suggests that relative permeability of organic cations is a complex function of the size, charge, and polarity of these residues and cation substrates. As judged by effects on macroscopic conductance, charged residues of the DEKA locus also appear to play a role in the mechanisms of block by external Ca2+ and H+, but are not essential for the positive shift in activation voltage that is produced by these ions.
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Wüstenberg, Daniel G., Milena Boytcheva, Bernd Grünewald, John H. Byrne, Randolf Menzel, and Douglas A. Baxter. "Current- and Voltage-Clamp Recordings and Computer Simulations of Kenyon Cells in the Honeybee." Journal of Neurophysiology 92, no. 4 (October 2004): 2589–603. http://dx.doi.org/10.1152/jn.01259.2003.
Повний текст джерелаАнотація:
The mushroom body of the insect brain is an important locus for olfactory information processing and associative learning. The present study investigated the biophysical properties of Kenyon cells, which form the mushroom body. Current- and voltage-clamp analyses were performed on cultured Kenyon cells from honeybees. Current-clamp analyses indicated that Kenyon cells did not spike spontaneously in vitro. However, spikes could be elicited by current injection in approximately 85% of the cells. Of the cells that produced spikes during a 1-s depolarizing current pulse, approximately 60% exhibited repetitive spiking, whereas the remaining approximately 40% fired a single spike. Cells that spiked repetitively showed little frequency adaptation. However, spikes consistently became broader and smaller during repetitive activity. Voltage-clamp analyses characterized a fast transient Na+ current ( INa), a delayed rectifier K+ current ( IK,V), and a fast transient K+ current ( IK,A). Using the neurosimulator SNNAP, a Hodgkin–Huxley-type model was developed and used to investigate the roles of the different currents during spiking. The model led to the prediction of a slow transient outward current ( IK,ST) that was subsequently identified by reevaluating the voltage-clamp data. Simulations indicated that the primary currents that underlie spiking are INa and IK,V, whereas IK,A and IK,ST primarily determined the responsiveness of the model to stimuli such as constant or oscillatory injections of current.
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Modabbernia, Mohammad Reza, Alireza Akoushideh, and Seyed Yaser Fakhrmoosavi. "Design and Analysis of the Voltage Controller for the Non Isolated Boost DC-DC Convertor." EMITTER International Journal of Engineering Technology 7, no. 1 (June 15, 2019): 14–33. http://dx.doi.org/10.24003/emitter.v7i1.312.
Повний текст джерелаАнотація:
In this paper, a controller has been presented by the root locus method based on the state space average model of the boost switching regulator with all of the converter’s parameters and uncertainties. In this model, the load current is unknown and the inductor, capacitor, diode and active switch are non ideal and have an on-state resistance. Furthermore, an on-state voltage drop has been considered for diode and active switch. By neglecting the load current and assuming the ideal elements the simplified model of the regulator has been caddied out. By these complete and simplified models, a step by step method has been proposed to design a single input single output (SISO), second order controller based on roots locus method. In this regard the controller's electronic circuit has been introduced by operational amplifiers. At the end, by simulation of the complete closed-loop system in MATLAB Simulink environment and comparing its results by the results of the regulator and controller circuits in PLECS, the accuracy of the designed controller performance has been shown.
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Osmanović, S. S., and S. A. Shefner. "gamma-Aminobutyric acid responses in rat locus coeruleus neurones in vitro: a current-clamp and voltage-clamp study." Journal of Physiology 421, no. 1 (February 1, 1990): 151–70. http://dx.doi.org/10.1113/jphysiol.1990.sp017938.
Повний текст джерела
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Mulolani, Francis, Francis Kafata, and Esau Zulu. "Design and Control of a Grid-connected Seven Level Inverter for Photovoltaic Applications." Zambia ICT Journal 3, no. 1 (March 7, 2019): 21–27. http://dx.doi.org/10.33260/zictjournal.v3i1.72.
Повний текст джерелаАнотація:
This paper presents the design and closed-loop current control of a grid connected seven-level, 3-phase diode-clamped multilevel inverter for Photovoltaic (PV) applications. The proposed closed loop current control technique is based on the voltage-oriented proportional integral (PI) controller theory. The modulation technique used is level-shifted-carrier sinusoidal pulse width modulation (SPWM). The gain values of PI controller were selected to achieve good current quality and dynamic response. Grid synchronization was achieved by using a synchronous-reference frame phase-locked loop (SRF-PLL). Matlab/Simulink was used for the control system design and simulation. The simulation results show that a 1.34% total harmonic distortion (THD) of the output current was achieved which is within the allowable current distortion limits by international standards. The stability of the system was analyzed using pole-zero mapping and root locus.
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Zhang, Xiaoli, Ningren Cui, Zhongying Wu, Junda Su, Jyothirmayee S. Tadepalli, Sowmya Sekizar, and Chun Jiang. "Intrinsic membrane properties of locus coeruleus neurons in Mecp2-null mice." American Journal of Physiology-Cell Physiology 298, no. 3 (March 2010): C635—C646. http://dx.doi.org/10.1152/ajpcell.00442.2009.
Повний текст джерелаАнотація:
Rett syndrome caused by mutations in methyl-CpG-binding protein 2 ( Mecp2) gene shows abnormalities in autonomic functions in which brain stem norepinephrinergic systems play an important role. Here we present systematic comparisons of intrinsic membrane properties of locus coeruleus (LC) neurons between Mecp2−/Y and wild-type (WT) mice. Whole cell current clamp was performed in brain slices of 3- to 4-wk-old mice. Mecp2−/Y neurons showed stronger inward rectification and had shorter time constant than WT cells. The former was likely due to overexpression of inward rectifier K+ (Kir)4.1 channel, and the latter was attributable to the smaller cell surface area. The action potential duration was prolonged in Mecp2−/Y cells with an extended rise time. This was associated with a significant reduction in the voltage-activated Na+ current density. After action potentials, >60% Mecp2−/Y neurons displayed fast and medium afterhyperpolarizations (fAHP and mAHP), while nearly 90% WT neurons showed only mAHP. The mAHP amplitude was smaller in Mecp2−/Y neurons. The firing frequency was higher in neurons with mAHP, and the frequency variation was greater in cells with both fAHP and mAHP in Mecp2−/Y mice. Small but significant differences in spike frequency adaptation and delayed excitation were found in Mecp2−/Y neurons. These results indicate that there are several electrophysiological abnormalities in LC neurons of Mecp2−/Y mice, which may contribute to the dysfunction of the norepinephrine system in Rett syndrome.
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Li, Yang, Rong Qi, Mingguang Dai, Xi Zhang, and Yiyun Zhao. "Linear Active Disturbance Rejection Control Strategy with Known Disturbance Compensation for Voltage-Controlled Inverter." Electronics 10, no. 10 (May 11, 2021): 1137. http://dx.doi.org/10.3390/electronics10101137.
Повний текст джерелаАнотація:
When the linear active disturbance rejection control (LADRC) is applied for the voltage-controlled inverter, the discrete period and the measurement noise limits the observer bandwidth, which affects the anti-disturbance performance of the system. This results in a poor ability to deal with the output voltage fluctuation under the load switch. In this paper, a novel LADRC strategy based on the known disturbance compensation is proposed for the voltage-controlled inverters. Firstly, the original LADRC scheme is designed. The dynamic performance and robustness of the system are analyzed by a root locus diagram, and the anti-disturbance ability is studied through amplitude-frequency characteristics. Then the partial model information and the load current are treated as the known disturbance and introduced to the linear extended state observer (LESO) to improve observation accuracy. The difference in anti-disturbance performance with the original scheme is compared and the stability of the LESO and LADRC is analyzed. Finally, the effectiveness of the proposed scheme is verified by the simulation and experimental results.
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Babich, Olga, John Reeves, and Roman Shirokov. "Block of CaV1.2 Channels by Gd3+ Reveals Preopening Transitions in the Selectivity Filter." Journal of General Physiology 129, no. 6 (May 29, 2007): 461–75. http://dx.doi.org/10.1085/jgp.200709733.
Повний текст джерелаАнотація:
Using the lanthanide gadolinium (Gd3+) as a Ca2+ replacing probe, we investigated the voltage dependence of pore blockage of CaV1.2 channels. Gd+3 reduces peak currents (tonic block) and accelerates decay of ionic current during depolarization (use-dependent block). Because diffusion of Gd3+ at concentrations used (<1 μM) is much slower than activation of the channel, the tonic effect is likely to be due to the blockage that occurred in closed channels before depolarization. We found that the dose–response curves for the two blocking effects of Gd3+ shifted in parallel for Ba2+, Sr2+, and Ca2+ currents through the wild-type channel, and for Ca2+ currents through the selectivity filter mutation EEQE that lowers the blocking potency of Gd3+. The correlation indicates that Gd3+ binding to the same site causes both tonic and use-dependent blocking effects. The apparent on-rate for the tonic block increases with the prepulse voltage in the range −60 to −45 mV, where significant gating current but no ionic current occurs. When plotted together against voltage, the on-rates of tonic block (−100 to −45 mV) and of use-dependent block (−40 to 40 mV) fall on a single sigmoid that parallels the voltage dependence of the gating charge. The on-rate of tonic block by Gd3+ decreases with concentration of Ba2+, indicating that the apparent affinity of the site to permeant ions is about 1 mM in closed channels. Therefore, we propose that at submicromolar concentrations, Gd3+ binds at the entry to the selectivity locus and that the affinity of the site for permeant ions decreases during preopening transitions of the channel.
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Lee, Chun-Kwon, Gyu-Sub Lee, and Seung-Jin Chang. "Solution to Fault of Multi-Terminal DC Transmission Systems Based on High Temperature Superconducting DC Cables." Energies 14, no. 5 (February 26, 2021): 1292. http://dx.doi.org/10.3390/en14051292.
Повний текст джерелаАнотація:
In this paper, we developed the small-signal state-space (SS) model of hybrid multi-terminal high-voltage direct-current (HVDC) systems and fault localization method in a failure situation. The multi-terminal HVDC (MTDC) system is composed of two wind farm side voltage-source converters (VSCs) and two grid side line-commutated converters (LCCs). To utilize relative advantages of the conventional line-commutated converter (LCC) and the voltage source converter (VSC) technologies, hybrid multi-terminal high-voltage direct-current (MTDC) technologies have been highlighted in recent years. For the models, grid side LCCs adopt distinct two control methods: master–slave control mode and voltage droop control mode. By utilizing root-locus analysis of the SS models for the hybrid MTDC system, we compare stability and responses of the target system according to control method. Furthermore, the proposed SS models are utilized in time-domain simulation to illustrate difference between master–slave control method and voltage droop control method. However, basic modeling method for hybrid MTDC system considering superconducting DC cables has not been proposed. In addition, when a failure occurs in MTDC system, conventional fault localization method cannot detect the fault location because the MTDC system is a complex form including a branch point. For coping with a failure situation, we propose a fault localization method for MTDC system including branch points. We model the MTDC system based on the actual experimental results and simulate a variety of failure scenarios. We propose the fault localization topology on a branch cable system using reflectometry method. Through the simulation results, we verify the performance of fault localization. In conclusion, guidelines to select control method in implementing hybrid MTDC systems for integrating offshore wind farms and to cope with failure method are provided in this paper.
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Jiang, Jingya, Wei Wang, Xuezhi Wu, Fen Tang, Zhengwen Yang, and Xiangjun Li. "Analysis of Harmonic Resonance Characteristics in Grid-Connected LCL Virtual Synchronous Generator." Sustainability 13, no. 8 (April 12, 2021): 4261. http://dx.doi.org/10.3390/su13084261.
Повний текст джерелаАнотація:
The virtual synchronous generator (VSG), which emulates the essential behavior of the conventional synchronous generator, has attracted great attention. This paper proposes to analyze the harmonic resonance characteristics in VSG using the state-space model. The analysis is based on a full-order state-space small-signal model that fully considers the dynamic of the inner loops and the VSG-based outer power control loop. Participation analysis is used to point out the contributions of different states to the eigenvalues. Moreover, eigenvalue locus and singular value decomposition (SVD) are applied together to evaluate the impact of the inner loop parameters on the harmonic resonance characteristics around the LCL filter resonance frequency. The analysis indicates that the harmonic resonance instability is mainly caused by decreasing the proportional gains of the current loop and the voltage loop. Finally, extensive numerical simulation and experimental results are given to verify the validity of the theoretical analysis. Both the simulation and experimental results indicate that the voltage of the common coupling point is unstable after decreasing the proportional gains of the current and voltage controllers. As Kpc decreases from 5 to 0.4 or Kpv decreases from 0.6 to 0.2, the harmonic distortion factor (HDF) around the LCL filter resonance frequency increases. Furthermore, the consistency of simulation results, experimental results, and the theoretical analysis results is validated.
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Glaum, S. R., and P. A. Brooks. "Tetanus-induced sustained potentiation of monosynaptic inhibitory transmission in the rat medulla: evidence for a presynaptic locus." Journal of Neurophysiology 76, no. 1 (July 1, 1996): 30–38. http://dx.doi.org/10.1152/jn.1996.76.1.30.
Повний текст джерелаАнотація:
1. Whole cell voltage-clamp recordings were made from dorsomedial nucleus tractus solitarii (dmNTS) neurons in coronal rat medullary slices. Synaptic activity was evoked by electrical stimulation in the region of the tractus solitarius (TS). Excitatory postsynaptic current/inhibitory postsynaptic current (EPSC/IPSC) complexes were recorded with K-gluconate-containing electrodes. Monosynaptic, gamma-aminobutyric acid-A (GABAA) receptor-mediated evoked IPSCs (evIPSCs) were recorded in the presence of D(-)2-amino-5-phosphonopentanoic acid (AP5, 50 microM) and 6,7-dinitroquinoxaline-2,3-dione (DNQX, 10 microM) with CsCl-containing electrodes. Control synaptic stimulation was applied at 0.1 Hz. 2. Tetanic stimulation (50 Hz, 2 s) produced an increase in the 10-90% rise time of the evIPSC component of mixed EPSC/IPSC complexes (assessed at Vhold = 0 mV) in three of eight recordings that remained significantly potentiated above control for > 15 min. This potentiation was further characterized with the use of Cs-containing electrodes. Tetanus similarly potentiated the amplitude of monosynaptic evIPSCs by 168.0 +/- 10.4% (mean +/- SE) control at 15 min posttetanus in 49 of 114 recordings. This tetanus-induced sustained potentiation of monosynaptic evIPSCs (TIP) was reproducible after recovery to control levels. 3. High Mg2+/low Ca2+ solutions reversibly blocked induction of TIP. TIP was reproducible in slices treated (> 7 min) with the N-type voltage-dependent Ca2+ channel (VDCC) antagonist omega-conotoxin-GVIA (1 microM) or L-type channel blocker nimodipine (10 microM), but not in those slices treated with either omega-agatoxin-IVA (200 nM, 20 min) or omega-conotoxin-MVIIC (2 microM). 4. The GABAB receptor antagonist CGP35348 (100 microM) reversibly blocked induction of TIP, reduced resting, and blocked tetanus-induced increases in spontaneous IPSC frequency. Spontaneous IPSC amplitude was unaffected by CGP35348. 5. These results suggest a presynaptic locus for TIP in dmNTS, which depends in part on Ca2+ influx through P/Q-type VDCCs.
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White, J. F., and C. F. Hinton. "Norepinephrine induces Na+-H+ and Cl -HCO3 exchange in Amphiuma intestine: locus and response to amiloride." American Journal of Physiology-Gastrointestinal and Liver Physiology 255, no. 1 (July 1, 1988): G18—G26. http://dx.doi.org/10.1152/ajpgi.1988.255.1.g18.
Повний текст джерелаАнотація:
Catecholamines stimulate Na+-dependent acid secretion by Amphiuma small intestine. Studies were undertaken to localize the response within the mucosa and characterize the effect on Na+ and Cl- transport. Stripped segments of jejunum were mounted in tissue chambers that permitted isolation of villus or intervillus epithelium. In Cl-free medium, norepinephrine (NE) stimulated the transepithelial voltage (Vms) in both villus and intervillus epithelium, whereas galactose and valine elevated Vms predominately in the villus. Paired segments of whole mucosa were maintained under short circuit while the rate of acid secretion (JH) was measured by titration of the unbuffered serosal medium and unidirectional fluxes of Na+ were measured by 22Na. NE significantly stimulated net Na+ absorption (JNanet), short circuit current (Isc), and JH. Amiloride reduced JH and Isc in NE-stimulated tissues and blocked the stimulation of JNanet by NE. The NE-induced current was nearly completely and reversibly inhibited by replacement of luminal medium HCO3- or CO2. NE significantly stimulated net Cl- absorption without changing Isc or JH. It is concluded that cells throughout the mucosa respond to catecholamines with enhanced Na+ and Cl- absorption, possibly through induction or stimulation of Na+-H+ and Cl- -HCO3- exchange.
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Ahern, Christopher A., Jian Payandeh, Frank Bosmans, and Baron Chanda. "The hitchhiker’s guide to the voltage-gated sodium channel galaxy." Journal of General Physiology 147, no. 1 (December 28, 2015): 1–24. http://dx.doi.org/10.1085/jgp.201511492.
Повний текст джерелаАнотація:
Eukaryotic voltage-gated sodium (Nav) channels contribute to the rising phase of action potentials and served as an early muse for biophysicists laying the foundation for our current understanding of electrical signaling. Given their central role in electrical excitability, it is not surprising that (a) inherited mutations in genes encoding for Nav channels and their accessory subunits have been linked to excitability disorders in brain, muscle, and heart; and (b) Nav channels are targeted by various drugs and naturally occurring toxins. Although the overall architecture and behavior of these channels are likely to be similar to the more well-studied voltage-gated potassium channels, eukaryotic Nav channels lack structural and functional symmetry, a notable difference that has implications for gating and selectivity. Activation of voltage-sensing modules of the first three domains in Nav channels is sufficient to open the channel pore, whereas movement of the domain IV voltage sensor is correlated with inactivation. Also, structure–function studies of eukaryotic Nav channels show that a set of amino acids in the selectivity filter, referred to as DEKA locus, is essential for Na+ selectivity. Structures of prokaryotic Nav channels have also shed new light on mechanisms of drug block. These structures exhibit lateral fenestrations that are large enough to allow drugs or lipophilic molecules to gain access into the inner vestibule, suggesting that this might be the passage for drug entry into a closed channel. In this Review, we will synthesize our current understanding of Nav channel gating mechanisms, ion selectivity and permeation, and modulation by therapeutics and toxins in light of the new structures of the prokaryotic Nav channels that, for the time being, serve as structural models of their eukaryotic counterparts.
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Hayar, Abdallah, Phillip M. Heyward, Thomas Heinbockel, Michael T. Shipley та Matthew Ennis. "Direct Excitation of Mitral Cells Via Activation of α1-Noradrenergic Receptors in Rat Olfactory Bulb Slices". Journal of Neurophysiology 86, № 5 (1 листопада 2001): 2173–82. http://dx.doi.org/10.1152/jn.2001.86.5.2173.
Повний текст джерелаАнотація:
The main olfactory bulb receives a significant modulatory noradrenergic input from the locus coeruleus. Previous in vivo and in vitro studies showed that norepinephrine (NE) inputs increase the sensitivity of mitral cells to weak olfactory inputs. The cellular basis for this action of NE is not understood. The goal of this study was to investigate the effect of NE and noradrenergic agonists on the excitability of mitral cells, the main output cells of the olfactory bulb, using whole cell patch-clamp recording in vitro. The noradrenergic agonists, phenylephrine (PE, 10 μM), isoproterenol (Isop, 10 μM), and clonidine (3 μM), were used to test for the functional presence of α1-, β-, and α2-receptors, respectively, on mitral cells. None of these agonists affected olfactory nerve (ON)–evoked field potentials recorded in the glomerular layer, or ON-evoked postsynaptic currents recorded in mitral cells. In whole cell voltage-clamp recordings, NE (30 μM) induced an inward current (54 ± 7 pA, n= 16) with an EC50 of 4.7 μM. Both PE and Isop also produced inward currents (22 ± 4 pA, n = 19, and 29 ± 9 pA, n = 8, respectively), while clonidine produced no effect ( n = 6). In the presence of TTX (1 μM), and blockers of excitatory and inhibitory fast synaptic transmission [gabazine 5 μM, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) 10 μM, and (±)-2-amino-5-phosphonopentanoic acid (APV) 50 μM], the inward current induced by PE persisted (EC50 = 9 μM), whereas that of Isop was absent. The effect of PE was also observed in the presence of the Ca2+ channel blockers, cadmium (100 μM) and nickel (100 μM). The inward current caused by PE was blocked when the interior of the cell was perfused with the nonhydrolyzable GDP analogue, GDPβS, indicating that the α1 effect is mediated by G-protein coupling. The current-voltage relationship in the absence and presence of PE indicated that the current induced by PE decreased near the equilibrium potential for potassium ions. In current-clamp recordings from bistable mitral cells, PE shifted the membrane potential from the downstate (−52 mV) toward the upstate (−40 mV), and significantly increased spike generation in response to perithreshold ON input. These findings indicate that NE excites mitral cells directly via α1 receptors, an effect that may underlie, at least in part, increased mitral cell responses to weak ON input during locus coeruleus activation in vivo.
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Preston, R. R., and C. Kung. "Isolation and characterization of paramecium mutants defective in their response to magnesium." Genetics 137, no. 3 (July 1, 1994): 759–69. http://dx.doi.org/10.1093/genetics/137.3.759.
Повний текст джерелаАнотація:
Abstract Four mutant strains of Paramecium tetraurelia with a reduced ability to respond behaviorally to Mg2+ have been isolated. Voltage-clamp analyses showed that their Mg2+ insensitivity is associated with a reduced Ca(2+)-dependent Mg2+ current. The four mutants, which have been doubled "eccentric," result from recessive mutations in two unlinked loci, xntA and xntB. Further analysis of xntA1 showed it to be unlinked to any of the behavioral mutants of P. tetraurelia described previously, but it is allelic to d4-521, a "K(+)-resistant" strain, and d4-596, a "Ba(2+)-shy" mutant. The varied pleiotropic effects of xntA1, which include increased resistance to Ni2+ and Zn2+ poisoning, suggest that the locus encodes a central regulator of cell function in Paramecium.
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Ali El-Sayed, Loai Mohamed, Doaa Khalil Ibrahim, Mahmoud Ibrahim Gilany, and Aboul’Fotouh El’Gharably. "An accurate technique for supervising distance relays during power swing." Indonesian Journal of Electrical Engineering and Computer Science 21, no. 3 (March 10, 2021): 1279. http://dx.doi.org/10.11591/ijeecs.v21.i3.pp1279-1290.
Повний текст джерелаАнотація:
Power swing is a power system transient phenomenon that arises due to several reasons including line switching, line outage, sudden increment or decrement in load, faults, etc. Unnecessary tripping during power swing and unnecessary blocking for faults occur during power swing result in distance relay maloperation. Several cascaded outages and major worldwide blackouts have occurred due to maloperation of distance relays. This paper proposes a technique for supervising distance relays during power swing. The proposed online technique discriminates real faults and power swing accurately. It relies on constructing a locus diagram for the current and voltage differences (∆I-∆V) between the two ends of the protected line. The locus is estimated at every power frequency cycle to continuously monitor the state of the line by utilizing the synchrophasor measurements at the sending and receiving ends of the line. The proposed technique is tested for two-area, four-machine power system under faults at different locations of zone-1 and zone-2 regions of distance relays, fault resistances, fault inception angles and slip frequencies using MATLAB software. The simulation results proved the superior improvement of distance relay performance for handling power swing blocking and unblocking actions.
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Ishimatsu, Masaru, Yuri Kidani, Akira Tsuda, and Takashi Akasu. "Effects of Methylphenidate on the Membrane Potential and Current in Neurons of the Rat Locus Coeruleus." Journal of Neurophysiology 87, no. 3 (March 1, 2002): 1206–12. http://dx.doi.org/10.1152/jn.00463.2001.
Повний текст джерелаАнотація:
Effects of methylphenidate (MPH), a therapeutic agent used in children presenting the attention deficit hyperactivity disorder (ADHD), on the membrane potential and current in neurons of the rat locus coeruleus (LC) were examined using intracellular and whole cell patch-clamp recording techniques. Application of MPH (30 μM) to artificial cerebrospinal fluid (ACSF) produced a hyperpolarizing response with amplitude of 12 ± 1 mV ( n = 29). Spontaneous firing of LC neurons was blocked during the MPH-induced hyperpolarization. Superfusion of LC neurons with ACSF containing 0 mM Ca2+ and 11 mM Mg2+ (Ca2+-free ACSF) produced a depolarizing response associated with an increase in spontaneous firing of the action potential. The MPH-induced hyperpolarization was blocked in Ca2+-free ACSF. Yohimbine (1 μM) and prazosin (10 μM), antagonists for α2 and α2B/2Creceptors, respectively, blocked the MPH-induced hyperpolarization in LC neurons. Tetrodotoxin (TTX, 1 μM) produced a partial depression of the MPH-induced hyperpolarization in LC neurons. Under the whole cell patch-clamp condition, MPH (30–300 μM) produced an outward current ( I MPH) with amplitude of 110 ± 6 pA ( n = 17) in LC neurons. The I MPH was blocked by Co2+ (1 mM). During prolonged application of MPH (300 μM for 45 min), the hyperpolarization gradually decreased in the amplitude and eventually disappeared, possibly because of depression of norepinephrine (NE) release from noradrenergic nerve terminals. At a low concentration (1 μM), MPH produced no outward current but consistently enhanced the outward current induced by NE. These results suggest that the MPH-induced response is mediated by NE via α2B/2C-adrenoceptors in LC neurons. I MPH was associated with an increase in the membrane conductance of LC neurons. The I MPH reversed its polarity at −102 ± 6 mV ( n = 8) in the ACSF. The reversal potential of I MPH was changed by 54 mV per decade change in the external K+ concentration. Current-voltage relationship showed that the I MPH exhibited inward rectification. Ba2+ (100 μM) suppressed the amplitude and the inward rectification of the I MPH.These results suggest that the I MPH is produced by activation of inward rectifier K+channels in LC neurons.
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Santin, Joseph M., and Lynn K. Hartzler. "Activation state of the hyperpolarization-activated current modulates temperature-sensitivity of firing in locus coeruleus neurons from bullfrogs." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 308, no. 12 (June 15, 2015): R1045—R1061. http://dx.doi.org/10.1152/ajpregu.00036.2015.
Повний текст джерелаАнотація:
Locus coeruleus neurons of anuran amphibians contribute to breathing control and have spontaneous firing frequencies that, paradoxically, increase with cooling. We previously showed that cooling inhibits a depolarizing membrane current, the hyperpolarization-activated current ( Ih) in locus coeruleus neurons from bullfrogs, Lithobates catesbeianus (Santin JM, Watters KC, Putnam RW, Hartzler LK. Am J Physiol Regul Integr Comp Physiol 305: R1451–R1464, 2013). This suggests an unlikely role for Ih in generating cold activation, but led us to hypothesize that inhibition of Ih by cooling functions as a physiological brake to limit the cold-activated response. Using whole cell electrophysiology in brain slices, we employed 2 mM Cs+ (an Ih antagonist) to isolate the role of Ih in spontaneous firing and cold activation in neurons recorded with either control or Ih agonist (cyclic AMP)-containing artificial intracellular fluid. Ih did not contribute to the membrane potential ( Vm) and spontaneous firing at 20°C. Although voltage-clamp analysis confirmed that cooling inhibits Ih, its lack of involvement in setting baseline firing and Vm precluded its ability to regulate cold activation as hypothesized. In contrast, neurons dialyzed with cAMP exhibited greater baseline firing frequencies at 20°C due to Ih activation. Our hypothesis was supported when the starting level of Ih was enhanced by elevating cAMP because cold activation was converted to more ordinary cold inhibition. These findings indicate that situations leading to enhancement of Ih facilitate firing at 20°C, yet the hyperpolarization associated with inhibiting a depolarizing cation current by cooling blunts the net Vm response to cooling to oppose normal cold-depolarizing factors. This suggests that the influence of Ih activation state on neuronal firing varies in the poikilothermic neuronal environment.
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Murai, Yoshinaka, Hitoshi Ishibashi, Susumu Koyama, and Norio Akaike. "Ca2+-Activated K+ Currents in Rat Locus Coeruleus Neurons Induced by Experimental Ischemia, Anoxia, and Hypoglycemia." Journal of Neurophysiology 78, no. 5 (November 1, 1997): 2674–81. http://dx.doi.org/10.1152/jn.1997.78.5.2674.
Повний текст джерелаАнотація:
Murai, Yoshinaka, Hitoshi Ishibashi, Susumu Koyama, and Norio Akaike. Ca2+-activated K+ currents in rat locus coeruleus neurons induced by experimental ischemia, anoxia, and hypoglycemia. J. Neurophysiol. 78: 2674–2681, 1997. The effects of metabolic inhibition on membrane currents and N-methyl-d-aspartic acid (NMDA)-induced currents were investigated in dissociated rat locus coeruleus (LC) neurons by using the nystatin perforated patch recording mode under voltage-clamp conditions. Changes in the intracellular Ca2+ concentration ([Ca2+]i) during the metabolic inhibition were also investigated by using the microfluometry with a fluorescent probe, Indo-1. Removal of both the oxygen and glucose (experimental ischemia), deprivation of glucose (hypoglycemia), and a blockade of electron transport by sodium cyanide (NaCN) or a reduction of the mitochondrial membrane potentialwith carbonyl cyanide- p-trifluoromethoxyphenyl-hydrazone(FCCP) as experimental anoxia all induced a slowly developing outward current ( I OUT) at a holding potential of −40 mV. The application of 10−4 M NMDA induced a rapid transient peak and a successive steady state inward current and a transient outward current immediately after washout. All treatments related to metabolic inhibition increased the NMDA-induced outward current( I NMDA-OUT) and prolonged the one-half recovery time of I NMDA-OUT. The reversal potentials of both I OUT and I NMDA-OUT were close to the K+ equilibrium potential ( E K) of −82 mV. Either charybdotoxin or tolbutamide inhibited the I OUT and I NMDA-OUT, suggesting the contribution of Ca2+-activated and ATP-sensitive K+ channels, even though the inhibitory effect of tolbutamide gradually diminished with time. Under the metabolic inhibition, the basal level of [Ca2+]i was increased and the one-half recovery time of the NMDA-induced increase in [Ca2+]i was prolonged. The I OUT induced by NaCN was inhibited by a continuous treatment of thapsigargin but not by ryanodine, indicating the involvement of inositol 1,4,5-trisphosphate (IP3)-induced Ca2+ release (IICR) store. These findings suggest that energy deficiency causes Ca2+ release from the IICR store and activates continuous Ca2+-activated K+ channels and transient ATP-sensitive K+ channels in acutely dissociated rat LC neurons.
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MORGANS, CATHERINE W., PHILIPPA R. BAYLEY, NICHOLAS W. OESCH, GAOYING REN, LAKSHMI AKILESWARAN, and W. ROWLAND TAYLOR. "Photoreceptor calcium channels: Insight from night blindness." Visual Neuroscience 22, no. 5 (September 2005): 561–68. http://dx.doi.org/10.1017/s0952523805225038.
Повний текст джерелаАнотація:
The genetic locus for incomplete congenital stationary night blindness (CSNB2) has been identified as the CACNA1f gene, encoding the α1F calcium channel subunit, a member of the L-type family of calcium channels. The electroretinogram associated with CSNB2 implicates α1F in synaptic transmission between retinal photoreceptors and bipolar cells. Using a recently developed monoclonal antibody to α1F, we localize the channel to ribbon active zones in rod photoreceptor terminals of the mouse retina, supporting a role for α1F in mediating glutamate release from rods. Detergent extraction experiments indicate that α1F is part of a detergent-resistant active zone complex, which also includes the synaptic ribbons. Comparison of native mouse rod calcium currents with recombinant α1F currents reveals that the current–voltage relationship for the native current is shifted approximately 30 mV to more hyperpolarized potentials than for the recombinant α1F current, suggesting modulation of the native channel by intracellular factors. Lastly, we present evidence for L-type α1D calcium channel subunits in cone terminals of the mouse retina. The presence of α1D channels in cones may explain the residual visual abilities of individuals with CSNB2.
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Schrader, Laura A., Yajun Ren, Feng Cheng, Dui Bui, J. David Sweatt, and Anne E. Anderson. "Kv4.2 is a locus for PKC and ERK/MAPK cross-talk." Biochemical Journal 417, no. 3 (January 16, 2009): 705–15. http://dx.doi.org/10.1042/bj20081213.
Повний текст джерелаАнотація:
Transient outward K+ currents are particularly important for the regulation of membrane excitability of neurons and repolarization of action potentials in cardiac myocytes. These currents are modulated by PKC (protein kinase C) activation, and the K+- channel subunit Kv4.2 is a major contributor to these currents. Furthermore, the current recorded from Kv4.2 channels expressed in oocytes is reduced by PKC activation. The mechanism underlying PKC regulation of Kv4.2 currents is unknown. In the present study, we determined that PKC directly phosphorylates the Kv4.2 channel protein. In vitro phosphorylation of the intracellular N- and C-termini of Kv4.2 GST (glutathione transferase) tagged fusion protein revealed that the C-terminal of Kv4.2 was phosphorylated by PKC, whereas the N-terminal was not. Amino acid mapping and site-directed mutagenesis revealed that the phosphorylated residues on the Kv4.2 C-terminal were Ser447 and Ser537. A phospho-site-specific antibody showed that phosphorylation at the Ser537 site was increased in the hippocampus in response to PKC activation. Surface biotinylation experiments revealed that mutation to alanine of both Ser447 and Ser537 in order to block phosphorylation at both of the PKC sites increased surface expression compared with wild-type Kv4.2. Electrophysiological recordings of the wild-type and both the alanine and aspartate mutant Kv4.2 channels expressed with KChIP3 (Kv4 channel-interacting protein 3) revealed no significant difference in the half-activation or half-inactivation voltage of the channel. Interestingly, Ser537 lies within a possible ERK (extracellular-signal-regulated kinase)/MAPK (mitogen-activated protein kinase) recognition (docking) domain in the Kv4.2 C-terminal sequence. We found that phosphorylation of Kv4.2 by PKC enhanced ERK phosphorylation of the channel in vitro. These findings suggest the possibility that Kv4.2 is a locus for PKC and ERK cross-talk.
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Geddada, Nagesh, and Mahesh Kumar Mishra. "LCL Filter with Active Damping using PI and SSI Regulators in Synchronous Rotating Reference Frame Current Controller for DSTATCOM." International Journal of Emerging Electric Power Systems 14, no. 4 (July 12, 2013): 309–26. http://dx.doi.org/10.1515/ijeeps-2013-0057.
Повний текст джерелаАнотація:
Abstract This article proposes a distribution static compensator (DSTATCOM) with interface LCL (inductor-capacitor-inductor) filter for load compensation in three-phase four-wire distribution system. DSTATCOM, consisting of voltage source inverter (VSI), is connected in parallel to the load and injects currents corresponding to load reactive, harmonic powers. But this injected current consists of unnecessary high-frequency switching ripple generated by VSI. This LCL filter has superior switching ripple attenuation capability compared to L filter. Moreover, this can be achieved with small value of overall LCL filter inductance than L filter. Thus providing high slew rate for output current to track the desired reference current closely, reducing voltage drop across it, as well as cost and size of filter. However, one major concern with LCL filter is its resonating frequency (determined from its L, C, L values), which can create high-resonance oscillating currents and results in improper load compensation. Therefore, in this study, proper design of LCL filter with high switching ripple attenuation and a current controller with proportional integral (PI) plus harmonic compensation (HC) regulators along with active damping feature of LCL filter in synchronous rotating reference (dq0) frame are presented. HC regulator minimizes the steady-state error in the non-sinusoidal filter currents (fundamental and harmonic) which are tracked by the VSI. Active damping feature (obtained by capacitor current feedback control of LCL filter) is used to overcome resonance oscillations and provides proper control, operation of DSTATCOM under steady-state and dynamic load conditions. Stability studies for designed LCL filter and current controller using Bode and root locus plots are also performed and presented. Extensive simulation study, to understand the compensation performance of LCL filter DSTATCOM with two types of current controllers (PI and PI plus HC) under steady-state and dynamic load conditions, is carried out in PSCAD simulator and the corresponding results along with THDs of various parameters are presented.
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Kobayashi, Yukari, Takuya Aoshima, Ryota Ito, Ryota Shinmura, Masato Ohtsuka, Eri Akasaka, Masahiro Sato, and Shuji Takabayashi. "Modification of i-GONAD Suitable for Production of Genome-Edited C57BL/6 Inbred Mouse Strain." Cells 9, no. 4 (April 13, 2020): 957. http://dx.doi.org/10.3390/cells9040957.
Повний текст джерелаАнотація:
Improved genome editing via oviductal nucleic acid delivery (i-GONAD) is a novel method for producing genome-edited mice in the absence of ex vivo handling of zygotes. i-GONAD involves the intraoviductal injection of clustered regularly interspaced short palindromic repeats (CRISPR) ribonucleoproteins via the oviductal wall of pregnant females at 0.7 days post-coitum, followed by in vivo electroporation (EP). Unlike outbred Institute of Cancer Research (ICR) and hybrid mouse strains, genome editing of the most widely used C57BL/6J (B6) strain with i-GONAD has been considered difficult but, recently, setting a constant current of 100 mA upon EP enabled successful i-GONAD in this strain. Unfortunately, the most widely used electroporators employ a constant voltage, and thus we explored conditions allowing the generation of a 100 mA current using two electroporators: NEPA21 (Nepa Gene Co., Ltd.) and GEB15 (BEX Co., Ltd.). When the current and resistance were set to 40 V and 350–400 Ω, respectively, the current was fixed to 100 mA. Another problem in using B6 mice for i-GONAD is the difficulty in obtaining pregnant B6 females consistently because estrous females often fail to be found. A single intraperitoneal injection of low-dose pregnant mare’s serum gonadotrophin (PMSG) led to synchronization of the estrous cycle of these mice. Consequently, approximately 51% of B6 females had plugs upon mating with males 2 days after PMSG administration, which contrasts with the case (≈26%) when B6 females were subjected to natural mating. i-GONAD performed on PMSG-treated pregnant B6 females under conditions of average resistance of 367 Ω and average voltage of 116 mA resulted in the production of pregnant females at a rate of 56% (5/9 mice), from which 23 fetuses were successfully delivered. Nine (39%) of these fetuses exhibited successful genome editing at the target locus.
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Pathan, E., S. A. Zulkifli, U. B. Tayab, and R. Jackson. "Small Signal Modeling of Inverter-based Grid-Connected Microgrid to Determine the Zero-Pole Drift Control with Dynamic Power Sharing Controller." Engineering, Technology & Applied Science Research 9, no. 1 (February 16, 2019): 3790–95. http://dx.doi.org/10.48084/etasr.2465.
Повний текст джерелаАнотація:
This paper presents a small signal state space modeling of three-phase inverter-based microgrid (MG) system with consideration of improved droop control. The complete system matrices for one distribution source-grid connects to the local load have been elaborated by applying high, medium and low-frequency clusters to the system without considering the switching action on the inverter during power-sharing. Moreover, the final matrices will be used to determine the location of the eigenvalues for the control parameters gains due to dynamic effect of the MG, by observing the root locus graph on cluster identification. Sensitivity analysis of all types of frequency cluster showed that power-sharing control parameters such as load current, source current, and inverter voltage are influencing system stability and must be considered when designing the proportional-integral (PI) control when different load scenarios have been applied from the zero-pole drifting. Those eigenvalues of the system model are indicating the frequency and damping oscillatory components when there is sudden changed at the inverter-grid connection. The matrices’ eigenvalues are being plotted using MATLAB/Simulink to identify system stability region and find the PI controller parameters.
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Krznar, Matija, Danijel Pavković, Mihael Cipek, and Juraj Benić. "Modeling, Controller Design and Simulation Groundwork on Multirotor Unmanned Aerial Vehicle Hybrid Power Unit." Energies 14, no. 21 (November 1, 2021): 7125. http://dx.doi.org/10.3390/en14217125.
Повний текст джерелаАнотація:
This paper presents the results of modeling, control system design and simulation verification of a hybrid-electric drive topology suitable for power flow control within unmanned aerial vehicles (UAVs). The hybrid power system is based on the internal combustion engine (ICE) driving a brushless DC (BLDC) generator supplying the common DC bus used for power distribution within the aircraft. The overall control system features proportional-integral-derivative (PID) feedback control of the ICE rotational speed using a Luenberger estimator for engine-generator set rotational speed estimation. The BLDC generator active rectifier voltage and current are controlled by proportional-integral (PI) feedback controllers, augmented by estimator-based feed-forward load compensators. The overall control system design has been based on damping optimum criterion, which yields straightforward analytical expressions for controller and estimator parameters. The robustness to key process parameters variations is investigated by means of root-locus methodology, and the effectiveness of the proposed hybrid power unit control system is verified by means of comprehensive computer simulations.
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Pan, Yu-Zhen, De-Pei Li, Shao-Rui Chen та Hui-Lin Pan. "Activation of δ-Opioid Receptors Excites Spinally Projecting Locus Coeruleus Neurons Through Inhibition of GABAergic Inputs". Journal of Neurophysiology 88, № 5 (1 листопада 2002): 2675–83. http://dx.doi.org/10.1152/jn.00298.2002.
Повний текст джерелаАнотація:
Stimulation of the noradrenergic nucleus locus coeruleus (LC) releases norepinephrine in the spinal cord, which inhibits dorsal horn neurons and produces analgesia. Activation of this descending noradrenergic pathway also contributes to the analgesic action produced by systemic opioids. The δ-opioid receptors are present presynaptically in the LC. However, their functional role in the control of the activity of spinally projecting LC neurons remains uncertain. In this study, we tested the hypothesis that activation of presynaptic δ-opioid receptors excites spinally projecting LC neurons through inhibition of GABA release. Spinally projecting LC neurons were retrogradely labeled by a fluorescent dye, DiI, injected into the spinal dorsal horn of rats. Whole cell voltage- and current-clamp recordings were performed on DiI-labeled LC neurons in brain slices in vitro. Retrogradely labeled LC noradrenergic neurons were demonstrated by dopamine-β-hydroxylase immunofluorescence. [d-Pen2,d-Pen5]-enkephalin (DPDPE, 1 μM) significantly decreased the frequency of GABA-mediated miniature inhibitory postsynaptic currents (IPSCs) of nine DiI-labeled LC neurons from 2.1 ± 0.5 to 0.7 ± 0.2 Hz without altering their amplitude and the kinetics. On the other hand, the miniature excitatory postsynaptic currents (EPSC) of nine DiI-labeled LC neurons were not significantly altered by DPDPE. Furthermore, DPDPE significantly inhibited the amplitude of evoked IPSC but not EPSC in eight DiI-labeled LC neurons. Under the current-clamp condition, the firing activity in 9 of 11 DiI-labeled LC neurons was significantly increased by 1 μM DPDPE from 4.6 ± 0.7 to 6.2 ± 1.0 Hz. Bicuculline (20 μM) also significantly increased the firing frequency in 13 of 20 neurons from 1.8 ± 0.5 to 2.8 ± 0.6 Hz. Additionally, the excitatory effect of DPDPE on LC neurons was diminished in the presence of bicuculline. Collectively, these data strongly suggest that activation of presynaptic δ-opioid receptors by DPDPE excites a population of spinally projecting LC neurons by preferential inhibition of GABA release. Thus presynaptic δ-opioid receptors likely play an important role in the regulation of the excitability of spinally projecting LC neurons and the descending noradrenergic inhibitory system.
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Liu, Sheng, Peng Su, and Lanyong Zhang. "A Nonlinear Disturbance Observer Based Virtual Negative Inductor Stabilizing Strategy for DC Microgrid with Constant Power Loads." Energies 11, no. 11 (November 15, 2018): 3174. http://dx.doi.org/10.3390/en11113174.
Повний текст джерелаАнотація:
For the dc microgrid system with constant power loads (CPLs), the dc bus voltage can easily cause high-frequency oscillation owing to the complicated impedance interactions. The large line inductance and the CPL-side capacitance will form an undamped LC circuit on the dc bus, which, together with the CPL, will make the system fall into the negative-damping region, thus causing the system instability. To address this problem, a virtual negative inductor (VNI) is built on the source side converter in this paper, which can effectively counteract the large line inductance, thus alleviating the instability problem. Moreover, a nonlinear disturbance observer (NDO) is proposed for estimating the converter output current, which relieves the strong dependence of the proposed VNI strategy on the output current measurement. And the proposed strategy is implemented in a totally decentralized manner, thus alleviating the single-point-failure problem in the central controller. For assuring the optimal parameter value for the proposed stabilizing strategy, a system root-locus diagram based parameter designing approach is adopted. And comparative Nyquist diagram based stability analyses are taken for studying the robustness of the proposed strategy to the system perturbations. Finally, detailed real-time simulations are conducted for validating the effectiveness of the proposed stabilizing strategy.
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Moussa, Intissar, та Adel Khedher. "Software in-the-Loop Simulation of an Advanced SVM Technique for 2ϕ-Inverter Control Fed a TPIM as Wind Turbine Emulator". Electronics 11, № 2 (7 січня 2022): 187. http://dx.doi.org/10.3390/electronics11020187.
Повний текст джерелаАнотація:
An appropriate modulation scheme selection ensures inverter performance. Thus, space vector modulation (SVM) is more efficient and has its own distinct advantages compared to other pulse width modulation (PWM) techniques. This work deals with the development of an advanced space vector pulse width modulation (SVM) technique for two-phase inverter control using an XSG library to ensure rapid prototyping of the controller FPGA implementation. The proposed architecture is applied digitally and in real time to drive a two-phase induction motor (TPIM) for small-scale wind turbine emulation (WTE) profiles in laboratories with minimum current ripple and torque oscillation. Four space voltage vectors generated for the used SVM technique do not contain a zero vector. Hence, for an adequate adjustment of these four vectors, a reference voltage vector located in the square locus is determined. Considering the asymmetry between the main and auxiliary windings, the TPIM behavior, which is fed through the advanced SVM controlled-two-phase inverter (2ϕ-inverter), is studied, allowing us to control the speed and the torque under different conditions for wind turbine emulation. Several quantities, such as electromagnetic torque, rotor fluxes, stator currents and speed, are analyzed. To validate the obtained results using both Simulink and XSG interfaces, the static and dynamic characteristics of the WTE are satisfactorily reproduced. The collected speed and torque errors between the reference and actual waveforms show low rates, proving emulator controller effectiveness.
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Qader, M. R. "Identifying the Optimal Controller Strategy for DC Motors." IAES International Journal of Robotics and Automation (IJRA) 6, no. 4 (December 1, 2017): 252. http://dx.doi.org/10.11591/ijra.v6i4.pp252-268.
Повний текст джерелаАнотація:
<p class="Default"><span>The aim of this study is to design a control strategy for the angular rate (speed) of a DC motor by varying the terminal voltage. This paper describes various designs for the control of direct current (DC) motors. We derive a transfer function for the system and connect it to a controller as feedback, taking the applied voltage as the system input and the angular velocity as the output. Different strategies combining proportional, integral, and derivative controllers along with phase lag compensators and lead integral compensators are investigated alongside the linear quadratic regulator. For each controller transfer function, the step response, root locus, and bode plot are analysed to ascertain the behaviour of the system, and the results are compared to identify the optimal strategy. It is found that the linear quadratic controller provides the best overall performance in terms of steady-state error, response time, and system stability. The purpose of the study that took place was to design the most appropriate controller for the steadiness of DC motors. Throughout this study, analytical means like tuning methods, loop control, and stability criteria were adopted. The reason for this was to suffice the preconditions and obligations. Furthermore, for the sake of verifying the legitimacy of the controller results, modelling by MATLAB and Simulink was practiced on every controller.</span></p>
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Goadsby, PJ. "How do the Currently Used Prophylactic Agents Work in Migraine?" Cephalalgia 17, no. 2 (April 1997): 85–92. http://dx.doi.org/10.1046/j.1468-2982.1997.1702085.x.
Повний текст джерелаАнотація:
Since migraine attacks are often frequent they require management with agents that reduce their number. Such agents, although often effective, are mechanistically ill-understood, They have been suggested to work through four main mechanisms, 5HT2 antagonism, modulation of plasma protein extravasation, modulation of central aminergic control mechanisms and membrane stabilizing effects through actions at voltage-sensitive channels. The evidence for these mechanisms, except plasma protein extravasation (see Cutrer, this supplement) is examined in the light of current thoughts concerning the pathophysiology of migraine. The understanding of the action of preventative drugs is at a relatively immature stage. Recent developments in pharmacology and studies of the pathophysiology of migraine have provided a substrate around which concepts can be developed. The actions and indeed the locus of action of the preventatives is crucial since these drugs are likely to point to the basic defect which underlies the process responsible for a migraine attack. Understanding this process can only facilitate patient management both in terms of explaining the disease and its implications and in controlling its clinical manifestations.
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Valencia-Rivera, Gerardo Humberto, Luis Ramon Merchan-Villalba, Guillermo Tapia-Tinoco, Jose Merced Lozano-Garcia, Mario Alberto Ibarra-Manzano, and Juan Gabriel Avina-Cervantes. "Hybrid LQR-PI Control for Microgrids under Unbalanced Linear and Nonlinear Loads." Mathematics 8, no. 7 (July 4, 2020): 1096. http://dx.doi.org/10.3390/math8071096.
Повний текст джерелаАнотація:
A hybrid Linear Quadratic Regulator (LQR) and Proportional-Integral (PI) control for a MicroGrid (MG) under unbalanced linear and nonlinear loads was presented and evaluated in this paper. The designed control strategy incorporates the microgrid behavior, low-cost LQR, and error reduction in the stationary state by the PI control, to reduce the overall energetic cost of the classical PI control applied to MGs. A Genetic Algorithm (GA) calculates the parameters of LQR with high-accuracy fitness function to obtain the optimal controller parameters as settling time and overshoot. The gain values of the classical PI controller were determined through the improved LQR values and geometrical root locus. When MG operates in the grid-tied mode under unbalanced conditions, the controller performance of the Current Source Inverter (CSI) of the MG is considerably affected. Consequently, the CSI operates in a negative-sequence mode to compensate for unbalanced current at the Point of Common Coupling (PCC) between the MG and the utility grid. The study cases involved the reduction of the negative-sequence percentage in the current at the PCC, mitigation of harmonics in the current signal injected by the MG, and close related power quality issues. All these cases have been analyzed by implementing an MG connected at the PCC of a low-voltage distribution network. A numerical model of the MG in Matlab/Simulink was implemented to verify the performance of the designed LQR-PI control to mitigate or overcome the power quality concerns. The extensive simulations have permitted verifying the robustness and effectiveness of the proposed strategy.
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Hoang, Q. V., D. Bajic, M. Yanagisawa, S. Nakajima, and Y. Nakajima. "Effects of Orexin (Hypocretin) on GIRK Channels." Journal of Neurophysiology 90, no. 2 (August 2003): 693–702. http://dx.doi.org/10.1152/jn.00001.2003.
Повний текст джерелаАнотація:
Orexins (hypocretins) are recently discovered excitatory transmitters implicated in arousal and sleep. Yet, their ionic and signal transduction mechanisms have not been fully clarified. Here we show that orexins suppress G-protein–coupled inward rectifier (GIRK) channel activity, and this suppression is likely to lead to neuronal excitation. Cultured neurons from the locus coeruleus (LC) and the nucleus tuberomammillaris (TM) were used, as well as HEK293A cells transfected with GIRK1 and 2, either human orexin receptor type 1 (OX1R) or type 2 (OX2R), mu opioid receptor and GFP cDNAs. In GTPγS-loaded cells, orexin A (OXA, 3 μM) inhibited GIRK currents that had previously been activated by somatostatin (in LC cells), nociceptin (TM cells), or the mu opioid agonist DAMGO (HEK cells). In guanosine triphosphate (GTP)–loaded HEK cells, in which GIRK currents were not preactivated, OXA induced a biphasic response through both types of orexin receptors: an initial current increase and a subsequent decrease to below resting levels. Current–voltage (I–V) relationships revealed that both the OXA-induced and suppressed currents are inwardly rectifying with reversal potentials around E K. The OXA-induced initial current was partially pertussis toxin (PTX) sensitive and partially PTX insensitive, whereas the OXA-suppressed current was PTX insensitive. These data suggest that orexin receptors couple with more than one type of G-protein, including PTX-sensitive (such as Gi/o) and PTX-insensitive (such as Gq/11) G-proteins. The modulation of GIRK channels by orexins may be one of the cellular mechanisms for the regulation of brain nuclei (e.g., LC and TM) that are crucial for arousal, sleep, and appetite.
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Pasquale, Eric Di, Karl D. Keegan, and Jeffrey L. Noebels. "Increased Excitability and Inward Rectification in Layer V Cortical Pyramidal Neurons in the Epileptic Mutant Mouse Stargazer." Journal of Neurophysiology 77, no. 2 (February 1, 1997): 621–31. http://dx.doi.org/10.1152/jn.1997.77.2.621.
Повний текст джерелаАнотація:
Di Pasquale, Eric, Karl D. Keegan, and Jeffrey L. Noebels. Increased excitability and inward rectification in layer V cortical pyramidal neurons in the epileptic mutant mouse stargazer. J. Neurophysiol. 77: 621–631, 1997. The excitability of layer V cortical pyramidal neurons was studied in vitro in the single-locus mutant mouse stargazer ( stg), a genetic model of spike wave epilepsy. Field recordings in neocortical slices from mutant mice bathed in artificial cerebrospinal fluid revealed spontaneous synchronous network discharges that were never present in wild-type slices. Intracellular and whole cell recordings from stg/ stg neurons in deep layers showed spontaneous giant depolarizing excitatory postsynaptic potentials generating bursts of action potentials, and a 78% reduction in the afterburst hyperpolarization. Whole cell recordings revealed gene-linked differences in active membrane properties in two types of regular spiking neurons. Single action potential rise and decay times were reduced, and the rheobase current was decreased by 68% in mutant cells. Plots of spike frequency-current relationships revealed that the gain of this relation was augmented by 29% in the mutant. Comparisons of visually identified pyramidal neuron firing properties in both genotypes revealed no difference in single action potential afterhyperpolarization. Voltage-clamp recordings showed an approximately threefold amplitude increase in a cesium-sensitive inward rectifier. No cell density or soma size differences were observed in the layer V pyramidal neuron population between the two genotypes. These results demonstrate an autonomous increase in cortical network excitability in a genetic epilepsy model. This defect could lower the threshold for aberrant thalamocortical spike wave oscillations in vivo, and may contribute to the mechanism of one form of inherited absence epilepsy.
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Jhamandas, Jack H., Frédéric Simonin, Jean-Jacques Bourguignon, and Kim H. Harris. "Neuropeptide FF and neuropeptide VF inhibit GABAergic neurotransmission in parvocellular neurons of the rat hypothalamic paraventricular nucleus." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 292, no. 5 (May 2007): R1872—R1880. http://dx.doi.org/10.1152/ajpregu.00407.2006.
Повний текст джерелаАнотація:
Neuropeptide FF (NPFF) and neuropeptide VF (NPVF) are octapeptides belonging to the RFamide family of peptides that have been implicated in a wide variety of physiological functions in the brain, including central autonomic and neuroendocrine regulation. The effects of these peptides are mediated via NPFF1 and NPFF2 receptors that are abundantly expressed in the rat brain, including the hypothalamic paraventricular nucleus (PVN), an autonomic nucleus critical for the secretion of neurohormones and the regulation of sympathetic outflow. In this study, we examined, using whole cell patch-clamp recordings in the brain slice, the effects of NPFF and NPVF on inhibitory GABAergic synaptic input to parvocellular PVN neurons. Under voltage-clamp conditions, NPFF and NPVF reversibly and in a concentration-dependent manner reduced the evoked bicuculline-sensitive inhibitory postsynaptic currents (IPSCs) in parvocellular PVN neurons by 25 and 31%, respectively. RF9, a potent and selective NPFF receptor antagonist, blocked NPFF-induced reduction of IPSCs. Recordings of miniature IPSCs in these neurons following NPFF and NPVF applications showed a reduction in frequency but not amplitude, indicating a presynaptic locus of action for these peptides. Under current-clamp conditions, NPVF and NPFF caused depolarization (6–9 mV) of neurons that persisted in the presence of TTX but was abolished in the presence of bicuculline. Collectively, these data provide evidence for a disinhibitory role of NPFF and NPVF in the hypothalamic PVN via an attenuation of GABAergic inhibitory input to parvocellular neurons of this nucleus and explain the central autonomic effects of NPFF.
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Kombian, Samuel B., Michiru Hirasawa, Didier Mouginot, Xihua Chen, and Quentin J. Pittman. "Short-Term Potentiation of Miniature Excitatory Synaptic Currents Causes Excitation of Supraoptic Neurons." Journal of Neurophysiology 83, no. 5 (May 1, 2000): 2542–53. http://dx.doi.org/10.1152/jn.2000.83.5.2542.
Повний текст джерелаАнотація:
Magnocellular neurons (MCNs) of the hypothalamic supraoptic nucleus (SON) secrete vasopressin and oxytocin. With the use of whole-cell and nystatin-perforated patch recordings of MCNs in current- and voltage-clamp modes, we show that high-frequency stimulation (HFS, 10–200 Hz) of excitatory afferents induces increases in the frequency and amplitude of 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo(f)quinoxaline-7-sulfonamide (NBQX)-sensitive miniature excitatory postsynaptic currents (mEPSCs) lasting up to 20 min. This synaptic enhancement, referred to as short-term potentiation (STP), could be induced repeatedly; required tetrodotoxin (TTX)-dependent action potentials to initiate, but not to maintain; and was independent of postsynaptic membrane potential, N-methyl-d-aspartate (NMDA) receptors, or retrograde neurohypophyseal neuropeptide release. STP was not accompanied by changes in the conductance of the MCNs or in the responsiveness of the postsynaptic non-NMDA receptors, as revealed by brief application of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate. mEPSCs showed similar rise times before and after HFS and analysis of amplitude distributions of mEPSCs revealed one or more peaks pre-HFS and the appearance of additional peaks post-HFS, which were equidistant from the first peak. STP of mEPSCs was not associated with enhanced evoked responses, but was associated with an NBQX-sensitive increase in spontaneous activity of MCNs. Thus we have identified a particularly long-lasting potentiation of excitatory synapses in the SON, which has a presynaptic locus, is dissociated from changes in evoked release, and which regulates postsynaptic cell excitability.
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Chen, X. H., I. Bezprozvanny, and R. W. Tsien. "Molecular basis of proton block of L-type Ca2+ channels." Journal of General Physiology 108, no. 5 (November 1, 1996): 363–74. http://dx.doi.org/10.1085/jgp.108.5.363.
Повний текст джерелаАнотація:
Hydrogen ions are important regulators of ion flux through voltage-gated Ca2+ channels but their site of action has been controversial. To identify molecular determinants of proton block of L-type Ca2+ channels, we combined site-directed mutagenesis and unitary current recordings from wild-type (WT) and mutant L-type Ca2+ channels expressed in Xenopus oocytes. WT channels in 150 mM K+ displayed two conductance states, deprotonated (140 pS) and protonated (45 pS), as found previously in native L-type Ca2+ channels. Proton block was altered in a unique fashion by mutation of each of the four P-region glutamates (EI-EIV) that form the locus of high affinity Ca2+ interaction. Glu(E)-->Gln(Q) substitution in either repeats I or III abolished the high-conductance state, as if the titration site had become permanently protonated. While the EIQ mutant displayed only an approximately 40 pS conductance, the EIIIQ mutant showed the approximately 40 pS conductance plus additional pH-sensitive transitions to an even lower conductance level. The EIVQ mutant exhibited the same deprotonated and protonated conductance states as WT, but with an accelerated rate of deprotonation. The EIIQ mutant was unusual in exhibiting three conductance states (approximately 145, 102, 50 pS, respectively). Occupancy of the low conductance state increased with external acidification, albeit much higher proton concentration was required than for WT. In contrast, the equilibrium between medium and high conductance levels was apparently pH-insensitive. We concluded that the protonation site in L-type Ca2+ channels lies within the pore and is formed by a combination of conserved P-region glutamates in repeats I, II, and III, acting in concert. EIV lies to the cytoplasmic side of the site but exerts an additional stabilizing influence on protonation, most likely via electrostatic interaction. These findings are likely to hold for all voltage-gated Ca2+ channels and provide a simple molecular explanation for the modulatory effect of H+ ions on open channel flux and the competition between H+ ions and permeant divalent cations. The characteristics of H+ interactions advanced our picture of the functional interplay between P-region glutamates, with important implications for the mechanism of Ca2+ selectivity and permeation.
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Grigg, J. J., T. Kozasa, Y. Nakajima, and S. Nakajima. "Single-channel properties of a G-protein-coupled inward rectifier potassium channel in brain neurons." Journal of Neurophysiology 75, no. 1 (January 1, 1996): 318–28. http://dx.doi.org/10.1152/jn.1996.75.1.318.
Повний текст джерелаАнотація:
1. In cultured rat locus coeruleus neurons, somatostatin or met-enkephalin induces an inwardly rectifying K+ conductance. This inward rectifier was analyzed at the single-channel level. 2. Using the inside-out patch-clamp, guanosine 5'-triphosphate (GTP) application to the cytoplasmic side in the presence of somatostatin or met-enkephalin in the pipette produced a large increase in channel activity, which disappeared on switching from GTP to guanosine 5'-diphosphate. 3. The unitary conductance was approximately 30 pS at -95 mV with an extracellular K+ concentration of 156 mM and an intracellular K+ concentration of 124 mM at 23 degrees C. The channel showed burst behavior, and the closed time histogram was fit by two exponentials, with the fast time constant being 0.4 ms. The burst time histogram was also fit by two exponentials, with time constants of 0.24 and 2.0 ms (at 10 nM somatostatin). When the somatostatin concentration was changed from 500 to 1 nM, the kinetic behavior of the channel did not change, except that the open probability of the patch was decreased. 4. The current-voltage relation of the unitary channel current showed inward rectification. The reversal potential coincided with the K+ equilibrium potential, and it shifted according to a change in the K+ equilibrium potential. 5. In the presence of external somatostatin, the application of guanosine 5'-O-(3-thiotriphosphate) to the cytoplasmic side induced an irreversible activation of this channel. 6. These results indicate that this K+ channel is the microscopic counterpart of the somatostatin- or met-enkephalin-induced inwardly rectifying K+ current in whole cell recording, and that the channel is activated by a G protein without a diffusible second messenger. Thus this channel is identified as a neuronal G-protein-coupled inward rectifier K+ channel. 7. Analysis of the burst behavior, based on a close-close-open kinetic model, revealed that there are at least four states in the K+ channel, a short gap, a longer closing, a short opening, and a long opening, and that the neuronal inward rectifier is activated at faster rates than the atrial inward rectifier.
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Pirone, Antonella, Johann Schredelseker, Petronel Tuluc, Elvira Gravino, Giuliana Fortunato, Bernhard E. Flucher, Antonella Carsana, Francesco Salvatore та Manfred Grabner. "Identification and functional characterization of malignant hyperthermia mutation T1354S in the outer pore of the Cavα1S-subunit". American Journal of Physiology-Cell Physiology 299, № 6 (грудень 2010): C1345—C1354. http://dx.doi.org/10.1152/ajpcell.00008.2010.
Повний текст джерелаАнотація:
To identify the genetic locus responsible for malignant hyperthermia susceptibility (MHS) in an Italian family, we performed linkage analysis to recognized MHS loci. All MHS individuals showed cosegregation of informative markers close to the voltage-dependent Ca2+ channel (CaV) α1S-subunit gene (CACNA1S) with logarithm of odds (LOD)-score values that matched or approached the maximal possible value for this family. This is particularly interesting, because so far MHS was mapped to >178 different positions on the ryanodine receptor (RYR1) gene but only to two on CACNA1S. Sequence analysis of CACNA1S revealed a c.4060A>T transversion resulting in amino acid exchange T1354S in the IVS5-S6 extracellular pore-loop region of CaVα1S in all MHS subjects of the family but not in 268 control subjects. To investigate the impact of mutation T1354S on the assembly and function of the excitation-contraction coupling apparatus, we expressed GFP-tagged α1ST1354S in dysgenic (α1S-null) myotubes. Whole cell patch-clamp analysis revealed that α1ST1354S produced significantly faster activation of L-type Ca2+ currents upon 200-ms depolarizing test pulses compared with wild-type GFP-α1S (α1SWT). In addition, α1ST1354S-expressing myotubes showed a tendency to increased sensitivity for caffeine-induced Ca2+ release and to larger action-potential-induced intracellular Ca2+ transients under low (≤2 mM) caffeine concentrations compared with α1SWT. Thus our data suggest that an additional influx of Ca2+ due to faster activation of the α1ST1354S L-type Ca2+ current, in concert with higher caffeine sensitivity of Ca2+ release, leads to elevated muscle contraction under pharmacological trigger, which might be sufficient to explain the MHS phenotype.
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Lasater, Eric M., Richard A. Normann, and Helga Kolb. "Signal integration at the pedicle of turtle cone photoreceptors: An anatomical and electrophysiological study." Visual Neuroscience 2, no. 6 (June 1989): 553–64. http://dx.doi.org/10.1017/s0952523800003497.
Повний текст джерелаАнотація:
AbstractThe morphology of the axon which connects the cell body and pedicle of turtle cone photoreceptors was studied by light and electron microscopy. The axon which contains numerous synaptic vesicles, some endoplasmic reticulum, and a few cisternae is basically filled with cytoplasm. The length of the axon is related to the class of cone and varies slightly with retinal location, with axons as short as 3–6 μm found in red cones, and as long as 60 μm in cones containing colorless oil droplets. By simultaneously voltage clamping the cell body and pedicle regions of single isolated cones, we measured the longitudinal axonal resistance and the cell body and pedicle membrane resistances. For each cell studied, the axonal resistance of cones with short axons was lower than the cell and pedicle membrane resistances. Thus, the cell can be considered to be an isopotential structure. However, in some cones with long axons, the axonal, cell body, and pedicle resistances were comparable. The pedicles of these cones, therefore, could act like summing points and may provide a locus for spatial signal integration. Electrical coupling between the principal and accessory members of double cones was also studied. Electron-microscopic observation of the membrane junction between the apposed inner segments of the double cones in the intact retina show narrow segments which resemble gap junctions. However, in every double cone studied in culture, passing currents into one member of the double cone did not result in measurable current flow in the adjacent cell. Thus, the two members of the double cone, isolated from the turtle retina, are not electrically coupled.
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Diallo, Moussa, Majidah Hamid-Adiamoh, Ousmane Sy, Pape Cheikh Sarr, Jarra Manneh, Mamadou Ousmane Ndiath, Oumar Gaye, et al. "Evolution of the Pyrethroids Target-Site Resistance Mechanisms in Senegal: Early Stage of the Vgsc-1014F and Vgsc-1014S Allelic Frequencies Shift." Genes 12, no. 12 (December 3, 2021): 1948. http://dx.doi.org/10.3390/genes12121948.
Повний текст джерелаАнотація:
The evolution and spread of insecticide resistance mechanisms amongst malaria vectors across the sub-Saharan Africa threaten the effectiveness and sustainability of current insecticide-based vector control interventions. However, a successful insecticide resistance management plan relies strongly on evidence of historical and contemporary mechanisms circulating. This study aims to retrospectively determine the evolution and spread of pyrethroid resistance mechanisms among natural Anopheles gambiae s.l. populations in Senegal. Samples were randomly drawn from an existing mosquito sample, collected in 2013, 2017, and 2018 from 10 sentinel sites monitored by the Senegalese National Malaria Control Programme (NMCP). Molecular species of An. gambiae s.l. and the resistance mutations at the Voltage-gated Sodium Channel 1014 (Vgsc-1014) locus were characterised using PCR-based assays. The genetic diversity of the Vgsc gene was further analyzed by sequencing. The overall species composition revealed the predominance of Anopheles arabiensis (73.08%) followed by An. gambiae s.s. (14.48%), Anopheles coluzzii (10.94%) and Anopheles gambiae–coluzii hybrids (1.48%). Both Vgsc-1014F and Vgsc-1014S mutations were found in all studied populations with a spatial variation of allele frequencies from 3% to 90%; and 7% to 41%, respectively. The two mutations have been detected since 2013 across all the selected health districts, with Vgsc-L1014S frequency increasing over the years while Vgsc-1014F decreasing. At species level, the Vgsc-1014F and Vgsc-1014S alleles were more frequent amongst An. gambiae s.s. (70%) and An. arabiensis (20%). The Vgsc gene was found to be highly diversified with eight different haplotypes shared between Vgsc-1014F and Vgsc-1014S. The observed co-occurrence of Vgsc-1014F and Vgsc-1014S mutations suggest that pyrethroid resistance is becoming a widespread phenomenon amongst malaria vector populations, and the NMCP needs to address this issue to sustain the gain made in controlling malaria.
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Smith, Carolyn L., Salsabil Abdallah, Yuen Yan Wong, Phuong Le, Alicia N. Harracksingh, Liana Artinian, Arianna N. Tamvacakis, Vincent Rehder, Thomas S. Reese, and Adriano Senatore. "Evolutionary insights into T-type Ca2+ channel structure, function, and ion selectivity from the Trichoplax adhaerens homologue." Journal of General Physiology 149, no. 4 (March 22, 2017): 483–510. http://dx.doi.org/10.1085/jgp.201611683.
Повний текст джерелаАнотація:
Four-domain voltage-gated Ca2+ (Cav) channels play fundamental roles in the nervous system, but little is known about when or how their unique properties and cellular roles evolved. Of the three types of metazoan Cav channels, Cav1 (L-type), Cav2 (P/Q-, N- and R-type) and Cav3 (T-type), Cav3 channels are optimized for regulating cellular excitability because of their fast kinetics and low activation voltages. These same properties permit Cav3 channels to drive low-threshold exocytosis in select neurons and neurosecretory cells. Here, we characterize the single T-type calcium channel from Trichoplax adhaerens (TCav3), an early diverging animal that lacks muscle, neurons, and synapses. Co-immunolocalization using antibodies against TCav3 and neurosecretory cell marker complexin labeled gland cells, which are hypothesized to play roles in paracrine signaling. Cloning and in vitro expression of TCav3 reveals that, despite roughly 600 million years of divergence from other T-type channels, it bears the defining structural and biophysical features of the Cav3 family. We also characterize the channel’s cation permeation properties and find that its pore is less selective for Ca2+ over Na+ compared with the human homologue Cav3.1, yet it exhibits a similar potent block of inward Na+ current by low external Ca2+ concentrations (i.e., the Ca2+ block effect). A comparison of the permeability features of TCav3 with other cloned channels suggests that Ca2+ block is a locus of evolutionary change in T-type channel cation permeation properties and that mammalian channels distinguish themselves from invertebrate ones by bearing both stronger Ca2+ block and higher Ca2+ selectivity. TCav3 is the most divergent metazoan T-type calcium channel and thus provides an evolutionary perspective on Cav3 channel structure–function properties, ion selectivity, and cellular physiology.
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Saitow, Fumihito, Shin'Ichiro Satake, Junko Yamada та Shiro Konishi. "β-Adrenergic Receptor-Mediated Presynaptic Facilitation of Inhibitory GABAergic Transmission at Cerebellar Interneuron-Purkinje Cell Synapses". Journal of Neurophysiology 84, № 4 (1 жовтня 2000): 2016–25. http://dx.doi.org/10.1152/jn.2000.84.4.2016.
Повний текст джерелаАнотація:
Norepinephrine (NE) has been shown to elicit long-term facilitation of GABAergic transmission to rat cerebellar Purkinje cells (PCs) through β-adrenergic receptor activation. To further examine the locus and adrenoceptor subtypes involved in the NE-induced facilitation of GABAergic transmission, we recorded inhibitory postsynaptic currents (IPSCs) evoked by focal stimulation with paired-pulse (PP) stimuli from PCs in rat cerebellar slices by whole cell recordings and analyzed the PP ratio of the IPSC amplitude. NE increased the IPSC amplitude with a decease in the variance of the PP ratio, which was mimicked by presynaptic manipulation of the transmission caused by increasing the extracellular Ca2+ concentration, confirming that the presynaptic adrenergic receptors are responsible for the facilitation. Pharmacological tests showed that the β2-adrenoceptor antagonist, ICI118,551, but not the β1-adrenoceptor antagonist, CGP20712A, blocked the NE-induced IPSC facilitation, suggesting that the β2-adrenoceptors on cerebellar interneurons, basket cells (BCs), mediate the noradrenergic facilitation of GABAergic transmission. Double recordings were performed from BCs and PCs to further characterize the regulation of the GABAergic synapses. First, on-cell recordings from BCs showed that the β-agonist isoproterenol (ISP) increased the frequencies of the spontaneous spikes in BCs and the spike-triggered IPSCs in PCs recorded with the whole cell mode. The amplitude of the spike-triggered IPSCs decreased or increased depending on the individual GABAergic synapses examined. Forskolin invariably increased both the amplitude and the frequency of the spike-triggered IPSCs. Double whole cell recordings from BC-PC pairs showed that ISP mainly caused an increase in the amplitude of the IPSCs evoked in the PCs by an action current in the BCs produced in response to voltage steps from −60 to −10 mV. Our data suggest that the noradrenergic facilitation of GABAergic transmission in the rat cerebellar cortex is mediated, at least in part, by depolarization and action potential discharges in the BCs through activation of the β2-adrenoceptors in BCs coupled to intracellular cyclic AMP formation.
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Benkenstein, C., M. Schmidt, and M. Gewecke. "Voltage-activated whole-cell K+ currents in lamina cells of the desert locust schistocerca gregaria." Journal of Experimental Biology 202, no. 14 (July 15, 1999): 1939–51. http://dx.doi.org/10.1242/jeb.202.14.1939.
Повний текст джерелаАнотація:
Voltage-dependent outward currents were studied in freshly dissociated somata of locust lamina cells. These currents were recorded in 142 somata using the whole-cell patch-clamp technique. By measuring the reversal potential at altered external [K+] and by replacing internal K+ with Cs+, we determined that the outward currents were carried by K+. The outward currents consist of a transient A-type K+ current (KA) and a delayed-rectifier-like K+ current (KD). Amongst the cells studied, we observed two distinct groups of cells. The most obvious difference between the two groups is that in group I cells the total outward current is dominated by KA (KA/KD=12.5), whereas in group II cells KA makes a smaller contribution (KA/KD=2.1). Furthermore, in cells of group I, the KA current shows a steeper voltage-dependence of activation, where VG50 is −29.9 mV and s is 11.9 (N=22), and inactivation, where VI50 is −84.5 mV and s is −6.3 (N=18), compared with the KA current in cells of group II: VG50=−7.9 mV; s=26.6 (N=36) and VI50=−68.4 mV; s=−7.5 (N=21) (VG50 is the voltage at which the whole-cell conductance G is half-maximally activated, VI50 is the voltage of half-maximal inactivation and s is the slope of the voltage-dependence). The transient KA current in group I cells decayed mono-exponentially. The decay of the KA current in group II cells was fitted with a double-exponential curve and was significantly faster than in group I cells. In contrast to the large differences in KA currents, the KD currents appeared to be quite similar in the two groups of cells.
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Laurent, G., K. J. Seymour-Laurent, and K. Johnson. "Dendritic excitability and a voltage-gated calcium current in locust nonspiking local interneurons." Journal of Neurophysiology 69, no. 5 (May 1, 1993): 1484–98. http://dx.doi.org/10.1152/jn.1993.69.5.1484.
Повний текст джерелаАнотація:
1. The active properties of axonless nonspiking interneurons in the thoracic nervous system of the locust Schistocerca americana were studied in vivo with the switched current-clamp technique from dendritic impalements, and in vitro with the whole-cell variation of the patch-clamp technique. 2. In 20% of in vivo recordings, depolarization of a dendrite to potentials more positive than about -40 mV evoked resonant behaviour and/or regenerative potentials. The latter were slow (half width: 20-30 ms), small (base-to-peak amplitude: 25-35 mV), and were often followed by a pronounced after hyperpolarization (AHP). 3. The slow regenerative potentials sometimes had multiple peaks separated by incomplete repolarizations. The voltage envelope of such potentials was always broader than that of spikes with single peaks. In other recordings, a same depolarizing pulse could evoke several regenerative potentials with different waveforms. These results suggested the presence of multiple dendritic initiation sites separated by regions of inexcitable membrane, allowing decremental conduction and the passive fusion of spike envelopes. 4. Graded active responses could also be evoked on rebound from short hyperpolarizations such as inhibitory postsynaptic potentials (IPSPs) provided that the membrane was already depolarized to about -40 mV. IPSPs evoked by several presynaptic interneurons differed in their ability to evoke rebound potentials suggesting that some synaptic sites were electrically closer than others to regions of active membrane. 5. Patch-clamp recordings from somata of nonspiking neurons isolated from 75% embryos and grown in culture medium for 1-2 days revealed the presence of an inactivating inward current resistant to 0.5-1 microM tetrodotoxin (TTX). The inward current was carried equally well by Ba2+, and sensitive to blockade by Cd2+ (0.5 mM), Ni2+ (0.75 mM), or Co2+ (2.5 mM). 6. The current activated around -40 mV, with voltage-dependent activation (time-to-peak approximately 20 ms at -35 mV and 1-2 ms at 0 mV). Tail currents evoked upon repolarization were well fitted by a single exponential (tau = 1-2 ms). Deactivation time constants shorter than 300 microseconds, however, could not be measured. 7. The current inactivated rapidly in a voltage-dependent manner, following two-exponential kinetics. A very small persistent component could be explained by the overlap between activation and inactivation curves, greatest at approximately -20 mV. The voltage of half-inactivation was about -25 mV. At a resting potential of -58 mV, 90% of the current was available for activation. Recovery from steady-state inactivation followed the sum of two or more exponential processes.(ABSTRACT TRUNCATED AT 400 WORDS)
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Scheller, Michaela, та Stuart A. Forman. "The γ Subunit Determines Whether Anesthetic-induced Leftward Shift Is Altered by a Mutation at α1S270 in α1β2γ2LGABAAReceptors". Anesthesiology 95, № 1 (1 липня 2001): 123–31. http://dx.doi.org/10.1097/00000542-200107000-00022.
Повний текст джерелаАнотація:
Background A major action of volatile anesthetics is enhancement of gamma-aminobutyric acid receptor type A (GABA(A)R) currents. In recombinant GABA(A)Rs consisting of several subunit mixtures, mutating the alpha1 subunit serine at position 270 to isoleucine [alpha1(S270I)] was reported to eliminate anesthetic-induced enhancement at low GABA concentrations. In the absence of studies at high GABA concentrations, it remains unclear whether alpha1(S270I) affects enhancement versus inhibition by volatile anesthetics. Furthermore, the majority of GABA(A)Rs in mammalian brain are thought to consist of alpha1, beta2, and gamma2 subunits, and the alpha1(S270I) mutation has not been studied in the context of this combination. Methods Recombinant GABA(A)Rs composed of alpha1beta2 or alpha1beta2gamma2L subunit mixtures were studied electrophysiologically in whole Xenopus oocytes in the voltage clamp configuration. Currents elicited by GABA (0.03 microM to 1 mM) were measured in the absence and presence of isoflurane or halothane. Anesthetic effects on GABA concentration responses were evaluated for individual oocytes. Results In wild-type alpha1beta2gamma2L GABA(A), anesthetics at approximately 2 minimum alveolar concentration (MAC) shifted GABA concentration response curves to the left approximately threefold, decreased the Hill coefficient, and enhanced currents at all GABA concentrations. The alpha1(S270I) mutation itself rendered the GABA(A)R more sensitive to GABA and reduced the Hill coefficient. At low GABA concentrations (EC5), anesthetic enhancement of peak current was much smaller in alpha1(S270I)beta2gamma2L versus wild-type channels. Paradoxically, the leftward shift of the whole GABA concentration-response relation by anesthetics was the same in both mutant and wild-type channels. At high GABA concentrations, volatile anesthetics reduced currents in alpha1(S270I)beta2gammaL GABA(A)Rs. In parallel studies on alpha1beta2 (gamma-less) GABA(A)Rs, anesthetic-induced leftward shifts in wild-type receptors were more than eightfold at 2 MAC, and the alpha1(S270I) mutation nearly eliminated anesthetic-induced leftward shift. Conclusions The results support a role for alpha1S270 in alpha1beta2gamma2L GABA(A)R gating and sensitivity to inhibition by volatile anesthetics. The alpha1S270 locus also modulates anesthetic enhancement in alpha1beta2 GABA(A)R. The presence of the gamma2L subunit reduces anesthetic-induced left shift of wild-type GABA(A)R and nullifies the impact of the alpha1(S2701) mutation on anesthetic modulation. Thus, the gamma2L subunit plays a significant role in GABA(A)R modulation by volatile anesthetic compounds.
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Yudaev, I., R. Kokurin, V. Eviev, B. Belyaeva, E. Sumyanova, and N. Romanyuk. "Usage of high voltage impulse generator to research the process of electropulse destruction of locust larvae in the soil." IOP Conference Series: Earth and Environmental Science 996, no. 1 (February 1, 2022): 012027. http://dx.doi.org/10.1088/1755-1315/996/1/012027.
Повний текст джерелаАнотація:
Abstract In accordance with announced technology, a laboratory research complex is needed for researching the influence of electropulse effects on locust larvae (capsules) and identification of the processing modes and construction design required to cause their irreversible (fatal) damage. In this regard, a schematic diagram of a laboratory research complex for electropulse processing has been developed and its structure has been determined. A separate question concerned a source of high voltage and a shaper of high-voltage impulses. A special design of a high-voltage impulse generator has been developed. This design can produce impact impulses of various durations - the impulse duration depends on the capacitive storage; with maximum amplitude of 16 kV and current per impulse of up to 400 A. The generator uses a capacitive storage discharge through a thyratron controlled by a microcontroller to the load. The proposed high-voltage impulse generator is necessary for researching the effect of electropulse high-voltage technology on the irreversible damage of locust larvae located in the soil layer, and for the experimental identification of the operating modes of the electrical part of the designed electrotechnological system, which allows for destruction of locust capsules directly in the field. The designed high-voltage generator was tested in operational mode when working with a load, which was the soil volume placed between the electrodes in the working chamber. The shape of the operational impulse and its parameters comply with predefined characteristics for electropulse cultivation of soil massif with locust larvae (capsules). After the tests, minor structural adjustments were made, and the generator itself was prepared for experimental studies in the laboratory.