Journal articles: 'Multi-ion channel'

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Gao, Jianzhao, Hong Wei, Alberto Cano, and Lukasz Kurgan. "PSIONplusm Server for Accurate Multi-Label Prediction of Ion Channels and Their Types." Biomolecules 10, no. 6 (June 7, 2020): 876. http://dx.doi.org/10.3390/biom10060876.

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Computational prediction of ion channels facilitates the identification of putative ion channels from protein sequences. Several predictors of ion channels and their types were developed in the last quindecennial. While they offer reasonably accurate predictions, they also suffer a few shortcomings including lack of availability, parallel prediction mode, single-label prediction (inability to predict multiple channel subtypes), and incomplete scope (inability to predict subtypes of the voltage-gated channels). We developed a first-of-its-kind PSIONplusm method that performs sequential multi-label prediction of ion channels and their subtypes for both voltage-gated and ligand-gated channels. PSIONplusm sequentially combines the outputs produced by three support vector machine-based models from the PSIONplus predictor and is available as a webserver. Empirical tests show that PSIONplusm outperforms current methods for the multi-label prediction of the ion channel subtypes. This includes the existing single-label methods that are available to the users, a naïve multi-label predictor that combines results produced by multiple single-label methods, and methods that make predictions based on sequence alignment and domain annotations. We also found that the current methods (including PSIONplusm) fail to accurately predict a few of the least frequently occurring ion channel subtypes. Thus, new predictors should be developed when a larger quantity of annotated ion channels will be available to train predictive models.

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Neyton, J., and M. Pelleschi. "Multi-ion occupancy alters gating in high-conductance, Ca(2+)-activated K+ channels." Journal of General Physiology 97, no. 4 (April 1, 1991): 641–65. http://dx.doi.org/10.1085/jgp.97.4.641.

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In this study, single-channel recordings of high-conductance Ca(2+)-activated K+ channels from rat skeletal muscle inserted into planar lipid bilayer were used to analyze the effects of two ionic blockers, Ba2+ and Na+, on the channel's gating reactions. The gating equilibrium of the Ba(2+)-blocked channel was investigated through the kinetics of the discrete blockade induced by Ba2+ ions. Gating properties of Na(+)-blocked channels could be directly characterized due to the very high rates of Na+ blocking/unblocking reactions. While in the presence of K+ (5 mM) in the external solution Ba2+ is known to stabilize the open state of the blocked channel (Miller, C., R. Latorre, and I. Reisin. 1987. J. Gen. Physiol. 90:427-449), we show that the divalent blocker stabilizes the closed-blocked state if permeant ions are removed from the external solution (K+ less than 10 microM). Ionic substitutions in the outer solution induce changes in the gating equilibrium of the Ba(2+)-blocked channel that are tightly correlated to the inhibition of Ba2+ dissociation by external monovalent cations. In permeant ion-free external solutions, blockade of the channel by internal Na+ induces a shift (around 15 mV) in the open probability--voltage curve toward more depolarized potentials, indicating that Na+ induces a stabilization of the closed-blocked state, as does Ba2+ under the same conditions. A kinetic analysis of the Na(+)-blocked channel indicates that the closed-blocked state is favored mainly by a decrease in opening rate. Addition of 1 mM external K+ completely inhibits the shift in the activation curve without affecting the Na(+)-induced reduction in the apparent single-channel amplitude. The results suggest that in the absence of external permeant ions internal blockers regulate the permeant ion occupancy of a site near the outer end of the channel. Occupancy of this site appears to modulate gating primarily by speeding the rate of channel opening.

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Roux, Benoît, Toby Allen, Simon Bernèche, and Wonpil Im. "Theoretical and computational models of biological ion channels." Quarterly Reviews of Biophysics 37, no. 1 (February 2004): 15–103. http://dx.doi.org/10.1017/s0033583504003968.

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1. Introduction 172. Dynamics of many-body systems 192.1 Effective dynamics of reduced systems 212.2 The constraint of thermodynamic equilibrium 242.3 Mean-field theories 253. Solvation free energy and electrostatics 273.1 Microscopic view of the Born model 273.2 Ion–Ion interactions in bulk solution 293.3 Continuum electrostatics and the PB equation 293.4 Limitations of continuum dielectric models 323.5 The dielectric barrier 333.6 The transmembrane potential and the PB-V equation 354. Statistical mechanical equilibrium theory 404.1 Multi-ion PMF 404.2 Equilibrium probabilities of occupancy 434.3 Coupling to the membrane potential 444.4 Ionic selectivity 484.5 Reduction to a one-dimensional (1D) free-energy profile 495. From MD toI–V: a practical guide 505.1 Extracting the essential ingredients from MD 515.1.1 Channel conductance from equilibrium and non-equilibrium MD 515.1.2 PMF techniques 525.1.3 Friction and diffusion coefficient techniques 535.1.4 About computational times 555.2 Ion permeation models 565.2.1 The 1D-NP electrodiffusion theory 565.2.2 Discrete-state Markov chains 575.2.3 The GCMC/BD algorithm 585.2.4 PNP electrodiffusion theory 626. Computational studies of ion channels 636.1 Computational studies of gA 656.1.1 Free-energy surface for K+ permeation 666.1.2 Mean-force decomposition 696.1.3 Cation-binding sites 696.1.4 Channel conductance 706.1.5 Selectivity 726.2 Computational studies of KcsA 726.2.1 Multi-ion free-energy surface and cation-binding sites 736.2.2 Channel conductance 746.2.3 Mechanism of ion conduction 776.2.4 Selectivity 786.3 Computational studies of OmpF 796.3.1 The need to compare the different level of approximations 796.3.2 Equilibrium protein fluctuations and ion distribution 806.3.3 Non-equilibrium ion fluxes 806.3.4 Reversal potential and selectivity 846.4 Successes and limitations 876.4.1 Channel structure 876.4.2 Ion-binding sites 876.4.3 Ion conduction 886.4.4 Ion selectivity 897. Conclusion 908. Acknowledgments 939. References 93The goal of this review is to establish a broad and rigorous theoretical framework to describe ion permeation through biological channels. This framework is developed in the context of atomic models on the basis of the statistical mechanical projection-operator formalism of Mori and Zwanzig. The review is divided into two main parts. The first part introduces the fundamental concepts needed to construct a hierarchy of dynamical models at different level of approximation. In particular, the potential of mean force (PMF) as a configuration-dependent free energy is introduced, and its significance concerning equilibrium and non-equilibrium phenomena is discussed. In addition, fundamental aspects of membrane electrostatics, with a particular emphasis on the influence of the transmembrane potential, as well as important computational techniques for extracting essential information from all-atom molecular dynamics (MD) simulations are described and discussed. The first part of the review provides a theoretical formalism to ‘translate’ the information from the atomic structure into the familiar language of phenomenological models of ion permeation. The second part is aimed at reviewing and contrasting results obtained in recent computational studies of three very different channels; the gramicidin A (gA) channel, which is a narrow one-ion pore (at moderate concentration), the KcsA channel from Streptomyces lividans, which is a narrow multi-ion pore, and the outer membrane matrix porin F (OmpF) from Escherichia coli, which is a trimer of three β-barrel subunits each forming wide aqueous multi-ion pores. Comparison with experiments demonstrates that current computational models are approaching semi-quantitative accuracy and are able to provide significant insight into the microscopic mechanisms of ion conduction and selectivity. We conclude that all-atom MD with explicit water molecules can represent important structural features of complex biological channels accurately, including such features as the location of ion-binding sites along the permeation pathway. We finally discuss the broader issue of the validity of ion permeation models and an outlook to the future.

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Hill, J. A., R. Coronado, and H. C. Strauss. "Potassium channel of cardiac sarcoplasmic reticulum is a multi-ion channel." Biophysical Journal 55, no. 1 (January 1989): 35–45. http://dx.doi.org/10.1016/s0006-3495(89)82778-x.

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5

Yue, D. T., and E. Marban. "Permeation in the dihydropyridine-sensitive calcium channel. Multi-ion occupancy but no anomalous mole-fraction effect between Ba2+ and Ca2+." Journal of General Physiology 95, no. 5 (May 1, 1990): 911–39. http://dx.doi.org/10.1085/jgp.95.5.911.

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We investigated the mechanism whereby ions cross dihydropyridine-sensitive (L-type) Ca channels in guinea pig ventricular myocytes. At the single-channel level, we found no evidence of an anomalous mole-fraction effect like that reported previously for whole-cell currents in mixtures of Ba and Ca. With the total concentration of Ba + Ca kept constant at 10 (or 110) mM, neither conductance nor absolute unitary current exhibits a paradoxical decrease when Ba and Ca are mixed, thereby weakening the evidence for a multi-ion permeation scheme. We therefore sought independent evidence to support or reject the multi-ion nature of the L-type Ca channel by measuring conductance at various permeant ion concentrations. Contrary to the predictions of models with only one binding site in the permeation pathway, single-channel conductance does not follow Michaelis-Menten kinetics as Ba activity is increased over three orders of magnitude. Two-fold variation in the Debye length of permeant ion solutions has little effect on conductance, making it unlikely that local surface charge effects could account for these results. Instead, the marked deviation from Michaelis-Menten behavior was best explained by supposing that the permeation pathway contains three or more binding sites that can be occupied simultaneously. The presence of three sites helps explain both a continued rise in conductance as [Ba2+] is increased above 110 mM, and the high single-channel conductance (approximately 7 pS) with 1 mM [Ba2+] as the charge carrier; the latter feature enables the L-type channel to carry surprisingly large currents at physiological divalent cation concentrations. Thus, despite the absence of an anomalous mole-fraction effect between Ba and Ca, we suggest that the L-type Ca channel in heart cells supports ion flux by a single-file, multi-ion permeation mechanism.

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García-Giménez, Elena, Antonio Alcaraz, and Vicente M. Aguilella. "Divalent Metal Ion Transport across Large Biological Ion Channels and Their Effect on Conductance and Selectivity." Biochemistry Research International 2012 (2012): 1–12. http://dx.doi.org/10.1155/2012/245786.

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Electrophysiological characterization of large protein channels, usually displaying multi-ionic transport and weak ion selectivity, is commonly performed at physiological conditions (moderate gradients of KCl solutions at decimolar concentrations buffered at neutral pH). We extend here the characterization of the OmpF porin, a wide channel of the outer membrane ofE. coli,by studying the effect of salts of divalent cations on the transport properties of the channel. The regulation of divalent cations concentration is essential in cell metabolism and understanding their effects is of key importance, not only in the channels specifically designed to control their passage but also in other multiionic channels. In particular, in porin channels like OmpF, divalent cations modulate the efficiency of molecules having antimicrobial activity. Taking advantage of the fact that the OmpF channel atomic structure has been resolved both in water and in MgCl2aqueous solutions, we analyze the single channel conductance and the channel selectivity inversion aiming to separate the role of the electrolyte itself, and the counterion accumulation induced by the protein channel charges and other factors (binding, steric effects, etc.) that being of minor importance in salts of monovalent cations become crucial in the case of divalent cations.

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Linsdell, Paul, Joseph A. Tabcharani, and John W. Hanrahan. "Multi-Ion Mechanism for Ion Permeation and Block in the Cystic Fibrosis Transmembrane Conductance Regulator Chloride Channel." Journal of General Physiology 110, no. 4 (October 1, 1997): 365–77. http://dx.doi.org/10.1085/jgp.110.4.365.

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The mechanism of Cl− ion permeation through single cystic fibrosis transmembrane conductance regulator (CFTR) channels was studied using the channel-blocking ion gluconate. High concentrations of intracellular gluconate ions cause a rapid, voltage-dependent block of CFTR Cl− channels by binding to a site ∼40% of the way through the transmembrane electric field. The affinity of gluconate block was influenced by both intracellular and extracellular Cl− concentration. Increasing extracellular Cl− concentration reduced intracellular gluconate affinity, suggesting that a repulsive interaction occurs between Cl− and gluconate ions within the channel pore, an effect that would require the pore to be capable of holding more than one ion simultaneously. This effect of extracellular Cl− is not shared by extracellular gluconate ions, suggesting that gluconate is unable to enter the pore from the outside. Increasing the intracellular Cl− concentration also reduced the affinity of intracellular gluconate block, consistent with competition between intracellular Cl− and gluconate ions for a common binding site in the pore. Based on this evidence that CFTR is a multi-ion pore, we have analyzed Cl− permeation and gluconate block using discrete-state models with multiple occupancy. Both two- and three-site models were able to reproduce all of the experimental data with similar accuracy, including the dependence of blocker affinity on external Cl− (but not gluconate) ions and the dependence of channel conductance on Cl− concentration. The three-site model was also able to predict block by internal and external thiocyanate (SCN−) ions and anomalous mole fraction behavior seen in Cl−/SCN− mixtures.

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Yu, Shijin, Wenzhen Zhu, Ying Wei, Jiahao Tong, Quanya Wei, Tianrui Chen, Xuannan He, Dingwen Hu, Cuiyun Li, and Hua Zhu. "Facile Synthesis of Multi-Channel Surface-Modified Amorphous Iron Oxide Nanospheres as High-Performance Anode Materials for Lithium-Ion Batteries." Energies 15, no. 16 (August 18, 2022): 5974. http://dx.doi.org/10.3390/en15165974.

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Based on the synergistic effect of ripening and hydrogen ion etching in a hydrothermal solution, a simple, facile, and low-cost new strategy was demonstrated to prepare multi-channel surface-modified amorphous Fe2O3 nanospheres as anodes for Li-ion batteries in this study. Compared with polycrystalline Fe2O3, the conversion reaction between amorphous Fe2O3 and lithium ions has a lower Gibbs free energy change and a stronger reversibility, which can contribute to an elevation in the cycle capability of the electrode. Meanwhile, there are abundant active sites and more effective dangling bonds/defects in amorphous materials, which is beneficial to promote charge transfer and lithium-ion migration kinetics. The Galvanostatic intermittent titration analysis results confirmed that the amorphous Fe2O3 electrode had a higher Li+ diffusion coefficient. In addition, the surfaces of the amorphous nanospheres are corroded to produce multiple criss-cross channels. The multi-channel surface structure can not only increase the contact area between Fe2O3 nanospheres and electrolyte, but also reserve space for volume expansion, thereby effectively alleviating the volume change during the intercalation-deintercalation of lithium ions. The electrochemical performance showed that the multi-channel surface-modified amorphous Fe2O3 electrode exhibited a higher specific capacity, a more stable cycle performance, and a narrower voltage hysteresis. It is believed that amorphous metal oxides have great potential as high-performance anodes of next-generation lithium-ion batteries.

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Hu, Gui Hua, Jun Ming Xu, Ji Jun Zhou, and Xiaoping Hu. "Design of Li-Ion Battery Management System Based on Atmega16." Applied Mechanics and Materials 263-266 (December 2012): 335–38. http://dx.doi.org/10.4028/www.scientific.net/amm.263-266.335.

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Due to the negative effect of li-ion battery monomer inconsistent performance in electric bicycle, a low-cost intelligent li-ion BMS (battery management system) is designed based on atmega16. Multi-channel analog switch and differential amplifier are used for multi-channel data acquisition, and the equalization circuit is used for the balance of each single cell. The results show that the design can realize the intelligent management of li-ion battery.

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Kuo, Chung-Chin, Wan-Yu Chen, and Ya-Chin Yang. "Block of Tetrodotoxin-resistant Na+ Channel Pore by Multivalent Cations." Journal of General Physiology 124, no. 1 (June 28, 2004): 27–42. http://dx.doi.org/10.1085/jgp.200409054.

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Tetrodotoxin-resistant (TTX-R) Na+ channels are much less susceptible to external TTX but more susceptible to external Cd2+ block than tetrodotoxin-sensitive (TTX-S) Na+ channels. Both TTX and Cd2+ seem to block the channel near the “DEKA” ring, which is probably part of a multi-ion single-file region adjacent to the external pore mouth and is involved in the selectivity filter of the channel. In this study we demonstrate that other multivalent transitional metal ions such as La3+, Zn2+, Ni2+, Co2+, and Mn2+ also block the TTX-R channels in dorsal root ganglion neurons. Just like Cd2+, the blocking effect has little intrinsic voltage dependence, but is profoundly influenced by Na+ flow. The apparent dissociation constants of the blocking ions are always significantly smaller in inward Na+ currents than those in outward Na+ current, signaling exit of the blocker along with the Na+ flow and a high internal energy barrier for “permeation” of these multivalent blocking ions through the pore. Most interestingly, the activation and especially the inactivation kinetics are slowed by the blocking ions. Moreover, the gating changes induced by the same concentration of a blocking ion are evidently different in different directions of Na+ current flow, but can always be correlated with the extent of pore block. Further quantitative analyses indicate that the apparent slowing of channel activation is chiefly ascribable to Na+ flow–dependent unblocking of the bound La3+ from the open Na+ channel, whereas channel inactivation cannot happen with any discernible speed in the La3+-blocked channel. Thus, the selectivity filter of Na+ channel is probably contiguous to a single-file multi-ion region at the external pore mouth, a region itself being nonselective in terms of significant binding of different multivalent cations. This region is “open” to the external solution even if the channel is “closed” (“deactivated”), but undergoes imperative conformational changes during the gating (especially the inactivation) process of the channel.

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Gibby, William A. T., Olena A. Fedorenko, Carlo Guardiani, Miraslau L. Barabash, Thomas Mumby, Stephen K. Roberts, Dmitry G. Luchinsky, and Peter V. E. McClintock. "Application of a Statistical and Linear Response Theory to Multi-Ion Na+ Conduction in NaChBac." Entropy 23, no. 2 (February 21, 2021): 249. http://dx.doi.org/10.3390/e23020249.

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Biological ion channels are fundamental to maintaining life. In this manuscript we apply our recently developed statistical and linear response theory to investigate Na+ conduction through the prokaryotic Na+ channel NaChBac. This work is extended theoretically by the derivation of ionic conductivity and current in an electrochemical gradient, thus enabling us to compare to a range of whole-cell data sets performed on this channel. Furthermore, we also compare the magnitudes of the currents and populations at each binding site to previously published single-channel recordings and molecular dynamics simulations respectively. In doing so, we find excellent agreement between theory and data, with predicted energy barriers at each of the four binding sites of ∼4,2.9,3.6, and 4kT.

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Wang, Chunni, Jun Ma, Bolin Hu, and Wuyin Jin. "Formation of multi-armed spiral waves in neuronal network induced by adjusting ion channel conductance." International Journal of Modern Physics B 29, no. 07 (March 2, 2015): 1550043. http://dx.doi.org/10.1142/s0217979215500435.

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The Hodgkin–Huxley neuron model is used to describe the local dynamics of nodes in a two-dimensional regular network with nearest-neighbor connections. Multi-armed spiral waves emerge when a group of spiral waves rotate the same core synchronously. Here we have numerically investigated how multi-armed spiral waves are formed in such a system. Under the appropriate conditions, multi-armed spiral waves were able to develop as a result of adjusting the conductance of ion channels of particular neurons in the network. In a realistic neuron model, it can be practiced by blocking potassium of ion channels embedded in the membrane of neurons. For example, decreasing the potassium channel conductance in some neurons with a certain transient period can lead to the development of a group of double spirals in a localized area of the network. Furthermore, decreasing the excitability and the external forcing current to zero led to the growth of these double spirals and the formation of a stable multi-armed spiral wave that occupied the network under inhomogeneity.

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Cai, Yong, Ji Wei Deng, and Tai Hong Wang. "Design of Multi-Channel Lithium-Ion Battery Test System." Advanced Materials Research 694-697 (May 2013): 1358–62. http://dx.doi.org/10.4028/www.scientific.net/amr.694-697.1358.

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At present, the Lithium-ion battery are the most used batteries in a large number of applications because of its high performances. It is important for Lithium-ion battery to make objective and accurate judgment to its performances before the practical application. A multi-channel high precision Lithium-ion battery test system, which could realize complex measure control, was designed in this paper. The system consists of upper computer (PC) and lower computer (control circuit unit). The communication between upper computer and lower computer is through RS-485 bus. The control circuit unit, which is mainly composed of micro-processor, control circuit, data acquisition circuit and protection circuit, can realize the function of testing Lithium-ion battery performances such as charging, discharging, internal resistance. Furthermore, based on actual use conditions it has shown that the system can accurately measure various Lithium-ion performance parameters and the current measurement accuracy can satisfy the test requirements.

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Tabcharani, Joseph A., Johanna M. Rommens, Yue-Xian Hou, Xiu-Bao Chang, Lap-Chee Tsui, John R. Riordan, and John W. Hanrahan. "Multi-ion pore behaviour in the CFTR chloride channel." Nature 366, no. 6450 (November 1993): 79–82. http://dx.doi.org/10.1038/366079a0.

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Huang, Hai, Michael K. Pugsley, Michael Accardi, Alexis Ascah, Roy Forster, and Simon Authier. "Simple Quantitative Comparison of Multi-Ion Channel Inhibition Profiles." Journal of Pharmacological and Toxicological Methods 88 (November 2017): 197–98. http://dx.doi.org/10.1016/j.vascn.2017.09.096.

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Cheng, Qian, and Ya Zhang. "Multi-Channel Graphite for High-Rate Lithium Ion Battery." Journal of The Electrochemical Society 165, no. 5 (2018): A1104—A1109. http://dx.doi.org/10.1149/2.1171805jes.

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Pansodtee, Pattawong, John Selberg, Manping Jia, Mohammad Jafari, Harika Dechiraju, Thomas Thomsen, Marcella Gomez, Marco Rolandi, and Mircea Teodorescu. "The multi-channel potentiostat: Development and evaluation of a scalable mini-potentiostat array for investigating electrochemical reaction mechanisms." PLOS ONE 16, no. 9 (September 16, 2021): e0257167. http://dx.doi.org/10.1371/journal.pone.0257167.

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A potentiostat is an essential piece of analytical equipment for studying electrochemical devices and reactions. As the design of electrochemical devices evolve, applications for systems with multiple working electrodes have become more common. These applications drive a need for low-cost multi-channel potentiostat systems. We have developed a portable, low-cost and scalable system with a modular design that can support 8 to 64 channels at a cost as low as $8 per channel. This design can replace the functionality of commercial potentiostats which cost upwards of $10k for certain applications. Each channel in the multi-channel potentiostat has an independent adjustable voltage source with a built-in ammeter and switch, making the device flexible for various configurations. The multi-channel potentiostat is designed for low current applications (nA range), but its purpose can change by varying its shunt resistor value. The system can either function as a standalone device or remotely controlled. We demonstrate the functionality of this system for the control of a 24-channel bioelectronic ion pump for open- and closed- loop control of pH.

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Correa, A. M., R. Latorre, and F. Bezanilla. "Ion permeation in normal and batrachotoxin-modified Na+ channels in the squid giant axon." Journal of General Physiology 97, no. 3 (March 1, 1991): 605–25. http://dx.doi.org/10.1085/jgp.97.3.605.

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Na+ permeation through normal and batrachotoxin (BTX)-modified squid axon Na+ channels was characterized. Unmodified and toxin-modified Na+ channels were studied simultaneously in outside-out membrane patches using the cut-open axon technique. Current-voltage relations for both normal and BTX-modified channels were measured over a wide range of Na+ concentrations and voltages. Channel conductance as a function of Na+ concentration curves showed that within the range 0.015-1 M Na+ the normal channel conductance is 1.7-2.5-fold larger than the BTX-modified conductance. These relations cannot be fitted by a simple Langmuir isotherm. Channel conductance at low concentrations was larger than expected from a Michaelis-Menten behavior. The deviations from the simple case were accounted for by fixed negative charges located in the vicinity of the channel entrances. Fixed negative charges near the pore mouths would have the effect of increasing the local Na+ concentration. The results are discussed in terms of energy profiles with three barriers and two sites, taking into consideration the effect of the fixed negative charges. Either single- or multi-ion pore models can account for all the permeation data obtained in both symmetric and asymmetric conditions. In a temperature range of 5-15 degrees C, the estimated Q10 for the conductance of the BTX-modified Na+ channel was 1.53. BTX appears not to change the Na+ channel ion selectively (for the conditions used) or the surface charge located near the channel entrances.

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Guet-McCreight, Alexandre, and Frances K. Skinner. "Computationally going where experiments cannot: a dynamical assessment of dendritic ion channel currents during in vivo-like states." F1000Research 9 (March 11, 2020): 180. http://dx.doi.org/10.12688/f1000research.22584.1.

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Background: Despite technological advances, how specific cell types are involved in brain function remains shrouded in mystery. Further, little is known about the contribution of different ion channel currents to cell excitability across different neuronal subtypes and their dendritic compartments in vivo. The picture that we do have is largely based on somatic recordings performed in vitro. Uncovering dendritic ion channel current contributions in neuron subtypes that represent a minority of the neuronal population is not currently a feasible task using purely experimental means. Methods: We employ two morphologically-detailed multi-compartment models of a specific type of inhibitory interneuron, the oriens lacunosum moleculare (OLM) cell. The OLM cell is a well-studied cell type in CA1 hippocampus that is important in gating sensory and contextual information. We create in vivo-like states for these cellular models by including levels of synaptic bombardment that would occur in vivo. Using visualization tools and analyses we assess the ion channel current contribution profile across the different somatic and dendritic compartments of the models. Results: We identify changes in dendritic excitability, ion channel current contributions and co-activation patterns between in vitro and in vivo-like states. Primarily, we find that the relative timing between ion channel currents are mostly invariant between states, but exhibit changes in magnitudes and decreased propagation across dendritic compartments. We also find enhanced dendritic hyperpolarization-activated cyclic nucleotide-gated channel (h-channel) activation during in vivo-like states, which suggests that dendritically located h-channels are functionally important in altering signal propagation in the behaving animal. Conclusions: Overall, we have demonstrated, using computational modelling, the dynamical changes that can occur to ion channel mechanisms governing neuronal spiking in vitro and in vivo. In particular, we have shown that the magnitudes of some ion channel current contributions are differentially altered during in vivo-like states relative to in vitro.

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Guet-McCreight, Alexandre, and Frances K. Skinner. "Computationally going where experiments cannot: a dynamical assessment of dendritic ion channel currents during in vivo-like states." F1000Research 9 (June 11, 2020): 180. http://dx.doi.org/10.12688/f1000research.22584.2.

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Background: Despite technological advances, how specific cell types are involved in brain function remains shrouded in mystery. Further, little is known about the contribution of different ion channel currents to cell excitability across different neuronal subtypes and their dendritic compartments in vivo. The picture that we do have is largely based on somatic recordings performed in vitro. Uncovering dendritic ion channel current contributions in neuron subtypes that represent a minority of the neuronal population is not currently a feasible task using purely experimental means. Methods: We employ two morphologically-detailed multi-compartment models of a specific type of inhibitory interneuron, the oriens lacunosum moleculare (OLM) cell. The OLM cell is a well-studied cell type in CA1 hippocampus that is important in gating sensory and contextual information. We create in vivo-like states for these cellular models by including levels of synaptic bombardment that would occur in vivo. Using visualization tools and analyses we assess the ion channel current contribution profile across the different somatic and dendritic compartments of the models. Results: We identify changes in dendritic excitability, ion channel current contributions and co-activation patterns between in vitro and in vivo-like states. Primarily, we find that the relative timing between ion channel currents are mostly invariant between states, but exhibit changes in magnitudes and decreased propagation across dendritic compartments. We also find enhanced dendritic hyperpolarization-activated cyclic nucleotide-gated channel (h-channel) activation during in vivo-like states, which suggests that dendritically located h-channels are functionally important in altering signal propagation in the behaving animal. Conclusions: Overall, we have demonstrated, using computational modelling, the dynamical changes that can occur to ion channel mechanisms governing neuronal spiking. Simultaneous access to dendritic compartments during simulated in vivo states shows that the magnitudes of some ion channel current contributions are differentially altered during in vivo-like states relative to in vitro.

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Gao, Jianzhao, Zhen Miao, Zhaopeng Zhang, Hong Wei, and Lukasz Kurgan. "Prediction of Ion Channels and their Types from Protein Sequences: Comprehensive Review and Comparative Assessment." Current Drug Targets 20, no. 5 (March 5, 2019): 579–92. http://dx.doi.org/10.2174/1389450119666181022153942.

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Background: Ion channels are a large and growing protein family. Many of them are associated with diseases, and consequently, they are targets for over 700 drugs. Discovery of new ion channels is facilitated with computational methods that predict ion channels and their types from protein sequences. However, these methods were never comprehensively compared and evaluated. Objective: We offer first-of-its-kind comprehensive survey of the sequence-based predictors of ion channels. We describe eight predictors that include five methods that predict ion channels, their types, and four classes of the voltage-gated channels. We also develop and use a new benchmark dataset to perform comparative empirical analysis of the three currently available predictors. Results: While several methods that rely on different designs were published, only a few of them are currently available and offer a broad scope of predictions. Support and availability after publication should be required when new methods are considered for publication. Empirical analysis shows strong performance for the prediction of ion channels and modest performance for the prediction of ion channel types and voltage-gated channel classes. We identify a substantial weakness of current methods that cannot accurately predict ion channels that are categorized into multiple classes/types. Conclusion: Several predictors of ion channels are available to the end users. They offer practical levels of predictive quality. Methods that rely on a larger and more diverse set of predictive inputs (such as PSIONplus) are more accurate. New tools that address multi-label prediction of ion channels should be developed.

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Payandeh, Jian. "Crystallographic studies of voltage-gated sodium and calcium channels." Acta Crystallographica Section A Foundations and Advances 70, a1 (August 5, 2014): C1488. http://dx.doi.org/10.1107/s2053273314085118.

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Voltage-gated ion channels (VGICs) mediate electrical signaling within the nervous system and regulate a wide range of physiological processes. Voltage-gated sodium (Nav) channels are responsible for initiating action potentials and their rapid activation, sodium selectivity, and drug sensitivity are unique among VGICs. Nav channels are the molecular targets of drugs used in local anaesthesia and in the treatment of genetic and sporadic Nav channelopathies including inherited epilepsy, migraine, periodic paralysis, cardiac arrhythmia, and chronic pain syndromes. Recent crystal structures of a Nav channel from the bacterium Arcobacter butzleri (NavAb) have revealed surprising insights into the structural basis for voltage-dependent activation, sodium selectivity, drug block, and slow inactivation (1,2). The available structures of NavAb will be described alongside complementary functional and molecular dynamic studies. Distinct from Nav channels, the closely related voltage-gated calcium (Cav) channels initiate processes such as synaptic transmission, muscle contraction, and hormone secretion in response to membrane depolarization. Cav channels catalyze the rapid and highly selective influx of calcium ions into cells despite a 70-fold higher extracellular concentration of sodium. By grafting a Cav channel selectivity filter onto NavAb, crystallographic and functional analyses of the resulting CavAb channel will be described that have revealed a multi-ion selectivity filter which establishes a structural framework for understanding the mechanisms of ion selectivity and conductance in vertebrate Cav channels (3).

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Stampe, Per, Jorge Arreola, Patricia Pérez-Cornejo, and Ted Begenisich. "Nonindependent K+ Movement through the Pore in IRK1 Potassium Channels." Journal of General Physiology 112, no. 4 (October 1, 1998): 475–84. http://dx.doi.org/10.1085/jgp.112.4.475.

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We measured unidirectional K+ in- and efflux through an inward rectifier K channel (IRK1) expressed in Xenopus oocytes. The ratio of these unidirectional fluxes differed significantly from expectations based on independent ion movement. In an extracellular solution with a K+ concentration of 25 mM, the data were described by a Ussing flux-ratio exponent, n′, of ∼2.2 and was constant over a voltage range from −50 to −25 mV. This result indicates that the pore of IRK1 channels may be simultaneously occupied by at least three ions. The IRK1 n′ value of 2.2 is significantly smaller than the value of 3.5 obtained for Shaker K channels under identical conditions. To determine if other permeation properties that reflect multi-ion behavior differed between these two channel types, we measured the conductance (at 0 mV) of single IRK1 channels as a function of symmetrical K+ concentration. The conductance could be fit by a saturating hyperbola with a half-saturation K+ activity of 40 mM, substantially less than the reported value of 300 mM for Shaker K channels. We investigated the ability of simple permeation models based on absolute reaction rate theory to simulate IRK1 current–voltage, conductance, and flux-ratio data. Certain classes of four-barrier, three-site permeation models are inconsistent with the data, but models with high lateral barriers and a deep central well were able to account for the flux-ratio and single channel data. We conclude that while the pore in IRK1 and Shaker channels share important similarities, including K+ selectivity and multi-ion occupancy, they differ in other properties, including the sensitivity of pore conductance to K+ concentration, and may differ in the number of K+ ions that can simultaneously occupy the pore: IRK1 channels may contain three ions, but the pore in Shaker channels can accommodate four or more ions.

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Barabash, M. L., W. A. T. Gibby, C. Guardiani, D. G. Luchinsky, and P. V. E. McClintock. "From the Potential of the Mean Force to a Quasiparticle’s Effective Potential in Narrow Ion Channels." Fluctuation and Noise Letters 18, no. 02 (May 29, 2019): 1940006. http://dx.doi.org/10.1142/s0219477519400066.

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We consider the selective permeation of ions through narrow water-filled channels in the presence of strong interaction between the ions. These interactions lead to highly correlated ionic motion, which can conveniently be described via the concept of a quasiparticle. Here, we connect the quasiparticle’s effective potential and the multi-ion potential of the mean force, found through molecular dynamics simulations, and we validate the method on an analytical toy model of the KcsA channel. Possible future applications of the method to the connection between molecular dynamical calculations and the experimentally measured current-voltage and current-concentration characteristics of the channel are discussed.

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Gibby, W. A. T., M. L. Barabash, C. Guardiani, D. G. Luchinsky, O. A. Fedorenko, S. K. Roberts, and P. V. E. McClintock. "Theory and Experiments on Multi-Ion Permeation and Selectivity in the NaChBac Ion Channel." Fluctuation and Noise Letters 18, no. 02 (May 29, 2019): 1940007. http://dx.doi.org/10.1142/s0219477519400078.

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The highly selective permeation of ions through biological ion channels is an unsolved problem of noise and fluctuations. In this paper, we motivate and introduce a non-equilibrium and self-consistent multi-species kinetic model, with the express aims of comparing with experimental recordings of current versus voltage and concentration and extracting important permeation parameters. For self-consistency, the behavior of the model at the two-state, i.e., selective limit in linear response, must agree with recent results derived from an equilibrium statistical theory. The kinetic model provides a good fit to data, including the key result of an anomalous mole fraction effect.

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Egwolf, Bernhard, and Benoît Roux. "Ion Selectivity of the KcsA Channel: A Perspective from Multi-Ion Free Energy Landscapes." Journal of Molecular Biology 401, no. 5 (September 2010): 831–42. http://dx.doi.org/10.1016/j.jmb.2010.07.006.

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Gamper, Nikita, and Shihab Shah. "Inferiority complex: why do sensory ion channels multimerize?" Biochemical Society Transactions 50, no. 1 (February 15, 2022): 213–22. http://dx.doi.org/10.1042/bst20211002.

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Peripheral somatosensory nerves are equipped with versatile molecular sensors which respond to acute changes in the physical environment. Most of these sensors are ion channels that, when activated, depolarize the sensory nerve terminal causing it to generate action potentials, which is the first step in generation of most somatic sensations, including pain. The activation and inactivation of sensory ion channels is tightly regulated and modulated by a variety of mechanisms. Amongst such mechanisms is the regulation of sensory ion channel activity via direct molecular interactions with other proteins in multi-protein complexes at the plasma membrane of sensory nerve terminals. In this brief review, we will consider several examples of such complexes formed around a prototypic sensory receptor, transient receptor potential vanilloid type 1 (TRPV1). We will also discuss some inherent conceptual difficulties arising from the multitude of reported complexes.

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Lin, N., M. G. Kivelson, R. L. McPherron, D. J. Williams, and T. A. Fritz. "Multi-point measurements of ULF wave phases using a multi-channel energetic ion detector." Advances in Space Research 8, no. 9-10 (January 1988): 437–41. http://dx.doi.org/10.1016/0273-1177(88)90157-3.

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Darszon, Alberto, Pedro Labarca, Takuya Nishigaki, and Felipe Espinosa. "Ion Channels in Sperm Physiology." Physiological Reviews 79, no. 2 (April 1, 1999): 481–510. http://dx.doi.org/10.1152/physrev.1999.79.2.481.

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Fertilization is a matter of life or death. In animals of sexual reproduction, the appropriate communication between mature and competent male and female gametes determines the generation of a new individual. Ion channels are key elements in the dialogue between sperm, its environment, and the egg. Components from the outer layer of the egg induce ion permeability changes in sperm that regulate sperm motility, chemotaxis, and the acrosome reaction. Sperm are tiny differentiated terminal cells unable to synthesize protein and difficult to study electrophysiologically. Thus understanding how sperm ion channels participate in fertilization requires combining planar bilayer techniques, in vivo measurements of membrane potential, intracellular Ca2+ and intracellular pH using fluorescent probes, patch-clamp recordings, and molecular cloning and heterologous expression. Spermatogenic cells are larger than sperm and synthesize the ion channels that will end up in mature sperm. Correlating the presence and cellular distribution of various ion channels with their functional status at different stages of spermatogenesis is contributing to understand their participation in differentiation and in sperm physiology. The multi-faceted approach being used to unravel sperm ion channel function and regulation is yielding valuable information about the finely orchestrated events that lead to sperm activation, induction of the acrosome reaction, and in the end to the miracle of life.

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Franciolini, F., and W. Nonner. "A multi-ion permeation mechanism in neuronal background chloride channels." Journal of General Physiology 104, no. 4 (October 1, 1994): 725–46. http://dx.doi.org/10.1085/jgp.104.4.725.

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Unitary current/voltage relationships of background Cl channels of rat hippocampal neurons were determined for varied gradients and absolute concentrations of NaCl. The channels revealed permeabilities for both Cl and Na ions. A hyperlinear increase of unitary conductance, observed for a symmetrical increase of salt concentration from 300 and 600 mM, indicated a multi-ion permeation mechanism. A variety of kinetic models of permeation were tested against the experimental current/voltage relationships. Models involving a pore occupied by mixed complexes of up to five ions were necessary to reproduce all measurements. A minimal model included four equilibrium states and four rate-limiting transitions, such that the empty pore accepts first an anion and then can acquire one or two cation/anion pairs. Three transport cycles are formed: a slow anion cycle (between the empty and single-anion states), a slow cation cycle (between the one- and three-ion states), and a fast anion cycle (between the three- and five-ion states). Thus, permeant anions are required for cation permeation, and several bound anions and cations promote a high rate of anion permeation. The optimized free-energy and electrical charge parameters yielded a self-consistent molecular interpretation, which can account for the particular order in which the pore accepts ions from the solutions. Although the model describes the mixed anion/cation permeability of the channel observed at elevated concentrations, it predicts a high selectivity for Cl anion at physiological ionic conditions.

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Picollet-Dhahan, Nathalie, Thomas Sordel, Stéphanie Garnier-Raveaud, Fabien Sauter, Florence Ricoul, Catherine Pudda, Frédérique Marcel, and François Chatelaina. "A Silicon-Based "Multi Patch" Device for Ion Channel Current Sensing." Sensor Letters 2, no. 2 (June 1, 2004): 91–94. http://dx.doi.org/10.1166/sl.2004.031.

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Huang, H., M. V. Accardi, K. Bujold, A. Ascah, S. Abtout, M. Pouliot, and S. Authier. "Data visualization in an era of multi-ion channel inhibition strategies." Journal of Pharmacological and Toxicological Methods 85 (May 2017): 90. http://dx.doi.org/10.1016/j.vascn.2017.02.015.

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Small, D., and C. Morris. "Pore properties of Lymnaea stagnalis neuron stretch-activated K+ channels." Journal of Experimental Biology 198, no. 9 (September 1, 1995): 1919–29. http://dx.doi.org/10.1242/jeb.198.9.1919.

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In many neurons, variations in membrane excitability are determined by a resting K+ conductance whose magnitude is modulated via neurotransmitters. The S-channel in Aplysia californica mechanosensory neurons is such a conductance, but it has also been shown to be a stretch-activated K+ channel. In this, it resembles stretch-activated K+ channels common to all molluscan neurons. Comparable channels are widespread, having been reported in molluscan and insect muscle and various vertebrate cells. The pore properties of the S-channel and similar stretch-activated K+ channels have received only sporadic attention. Here we examine, at the single-channel level, the permeation characteristics of a stretch-activated K+ channel from neurons of the mollusc Lymnaea stagnalis. MichaelisMenten constants (Km) for the conductance, obtained separately for inward (28 mmol l-1) and outward (91 mmol l-1) K+ currents, suggest that the channel presents to the external medium, where [K+] is lower, a higher-affinity site than it presents to the cytoplasmic medium. This may help to ensure that influx is not diffusion-limited at potentials near the resting potential, i.e. near the K+ equilibrium constant. Anomalous mole fraction behavior, observed when the ratio of permeant ion (K+ and Rb+) was varied, indicated that the stretch-activated K+ channel is a multi-ion pore. The ion selectivity sequence determined using reversal potentials under bi-ionic conditions was Cs+>K+>Rb+>NH4+>Na+>Li+, and using relative conductance in symmetrical solutions, the sequence was Tl+=K+>Rb+>NH4+>Na+=Li+=Cs+. Extreme variations in extracellular pH from 4.7 to 11.4 had no effect on stretch-activated K+ channel conductance, whereas normal concentrations of extracellular Mg2+ reduced inward K+ current. Intracellular, but not extracellular, Ba2+ produced a slow, open channel block with an IC50 of 140±80 µmol l-1. These pore properties are compared with those of other stretch-activated K+ channels and of K+ channels in general. In spite of a greater than half order of magnitude difference in the cytoplasmic [K+] in marine (Aplysia californica) and freshwater (Lymnaea stagnalis) molluscs, the conductances of stretch-activated K+ channels from the two groups are very similar.

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Ren, Qingjuan, Zhiqiang Shi, Lei Yan, Fuming Zhang, Linlin Fan, Lijun Zhang, and Wenjie Lv. "High-performance sodium-ion storage: multi-channel carbon nanofiber freestanding anode contrived via ingenious solvent-induced phase separation." Journal of Materials Chemistry A 8, no. 38 (2020): 19898–907. http://dx.doi.org/10.1039/d0ta04841k.

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Mironov, S. L. "Conformational model for ion permeation in membrane channels: a comparison with multi-ion models and applications to calcium channel permeability." Biophysical Journal 63, no. 2 (August 1992): 485–96. http://dx.doi.org/10.1016/s0006-3495(92)81628-4.

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Haug, Trude, Daniel Sigg, Sergio Ciani, Ligia Toro, Enrico Stefani, and Riccardo Olcese. "Regulation of K+ Flow by a Ring of Negative Charges in the Outer Pore of BKCa Channels. Part I." Journal of General Physiology 124, no. 2 (July 26, 2004): 173–84. http://dx.doi.org/10.1085/jgp.200308949.

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The pore region of the majority of K+ channels contains the highly conserved GYGD sequence, known as the K+ channel signature sequence, where the GYG is critical for K+ selectivity (Heginbotham, L., T. Abramson, and R. MacKinnon. 1992. Science. 258:1152–1155). Exchanging the aspartate residue with asparagine in this sequence abolishes ionic conductance of the Shaker K+ channel (D447N) (Hurst, R.S., L. Toro, and E. Stefani. 1996. FEBS Lett. 388:59–65). In contrast, we found that the corresponding mutation (D292N) in the pore forming α subunit (hSlo) of the voltage- and Ca2+-activated K+ channel (BKCa, MaxiK) did not prevent conduction but reduced single channel conductance. We have investigated the role of outer pore negative charges in ion conduction (this paper) and channel gating (Haug, T., R. Olcese, T. Ligia, and E. Stefani. 2004. J. Gen Physiol. 124:185–197). In symmetrical 120 mM [K+], the D292N mutation reduced the outward single channel conductance by ∼40% and nearly abolished inward K+ flow (outward rectification). This rectification was partially relieved by increasing the external K+ concentration to 700 mM. Small inward currents were resolved by introducing an additional mutation (R207Q) that greatly increases the open probability of the channel. A four-state multi-ion pore model that incorporates the effects of surface charge was used to simulate the essential properties of channel conduction. The conduction properties of the mutant channel (D292N) could be predicted by a simple ∼8.5-fold reduction of the surface charge density without altering any other parameter. These results indicate that the aspartate residue in the BKCa pore plays a key role in conduction and suggest that the pore structure is not affected by the mutation. We speculate that the negative charge strongly accumulates K+ in the outer vestibule close to the selectivity filter, thus increasing the rate of ion entry into the pore.

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Sugawara, Masao, Ayumi Hirano, Marián Rehák, Jun Nakanishi, Kunji Kawai, Hitoshi Sato, and Yoshio Umezawa. "Electrochemical evaluation of chemical selectivity of glutamate receptor ion channel proteins with a multi-channel sensor." Biosensors and Bioelectronics 12, no. 5 (January 1997): 425–39. http://dx.doi.org/10.1016/s0956-5663(97)00005-5.

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Polo-Parada, Luis, and Stephen J. Korn. "Block of N-type Calcium Channels in Chick Sensory Neurons by External Sodium." Journal of General Physiology 109, no. 6 (June 1, 1997): 693–702. http://dx.doi.org/10.1085/jgp.109.6.693.

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L-type Ca2+ channels select for Ca2+ over sodium Na+ by an affinity-based mechanism. The prevailing model of Ca2+ channel permeation describes a multi-ion pore that requires pore occupancy by at least two Ca2+ ions to generate a Ca2+ current. At [Ca2+] < 1 μM, Ca2+ channels conduct Na+. Due to the high affinity of the intrapore binding sites for Ca2+ relative to Na+, addition of μM concentrations of Ca2+ block Na+ conductance through the channel. There is little information, however, about the potential for interaction between Na+ and Ca2+ for the second binding site in a Ca2+ channel already occupied by one Ca2+. The two simplest possibilities, (a) that Na+ and Ca2+ compete for the second binding site or (b) that full time occupancy by one Ca2+ excludes Na+ from the pore altogether, would imply considerably different mechanisms of channel permeation. We are studying permeation mechanisms in N-type Ca2+ channels. Similar to L-type Ca2+ channels, N-type channels conduct Na+ well in the absence of external Ca2+. Addition of 10 μM Ca2+ inhibited Na+ conductance by 95%, and addition of 1 mM Mg2+ inhibited Na+ conductance by 80%. At divalent ion concentrations of 2 mM, 120 mM Na+ blocked both Ca2+ and Ba2+ currents. With 2 mM Ba2+, the IC50 for block of Ba2+ currents by Na+ was 119 mM. External Li+ also blocked Ba2+ currents in a concentration-dependent manner, with an IC50 of 97 mM. Na+ block of Ba2+ currents was dependent on [Ba2+]; increasing [Ba2+] progressively reduced block with an IC50 of 2 mM. External Na+ had no effect on voltage-dependent activation or inactivation of the channel. These data suggest that at physiological concentrations, Na+ and Ca2+ compete for occupancy in a pore already occupied by a single Ca2+. Occupancy of the pore by Na+ reduced Ca2+ channel conductance, such that in physiological solutions, Ca2+ channel currents are between 50 and 70% of maximal.

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Lu, Z., and R. MacKinnon. "A conductance maximum observed in an inward-rectifier potassium channel." Journal of General Physiology 104, no. 3 (September 1, 1994): 477–86. http://dx.doi.org/10.1085/jgp.104.3.477.

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One prediction of a multi-ion pore is that its conductance should reach a maximum and then begin to decrease as the concentration of permeant ion is raised equally on both sides of the membrane. A conductance maximum has been observed at the single-channel level in gramicidin and in a Ca(2+)-activated K+ channel at extremely high ion concentration (> 1,000 mM) (Hladky, S. B., and D. A. Haydon. 1972. Biochimica et Biophysica Acta. 274:294-312; Eisenmam, G., J. Sandblom, and E. Neher. 1977. In Metal Ligand Interaction in Organic Chemistry and Biochemistry. 1-36; Finkelstein, P., and O. S. Andersen. 1981. Journal of Membrane Biology. 59:155-171; Villarroel, A., O. Alvarez, and G. Eisenman. 1988. Biophysical Journal. 53:259a. [Abstr.]). In the present study we examine the conductance-concentration relationship in an inward-rectifier K+ channel, ROMK1. Single channels, expressed in Xenopus oocytes, were studied using inside-out patch recording in the absence of internal Mg2+ to eliminate blockade of outward current. Potassium, at equal concentrations on both sides of the membrane, was varied from 10 to 1,000 mM. As K+ was raised from 10 mM, the conductance increased steeply and reached a maximum value (39 pS) at 300 mM. The single-channel conductance then became progressively smaller as K+ was raised beyond 300 mM. At 1000 mM K+, the conductance was reduced to approximately 75% of its maximum value. The shape of the conductance-concentration curve observed in the ROMK1 channel implies that it has multiple K(+)-occupied binding sites in its conduction pathway.

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Shapiro, M. S., and T. E. DeCoursey. "Selectivity and gating of the type L potassium channel in mouse lymphocytes." Journal of General Physiology 97, no. 6 (June 1, 1991): 1227–50. http://dx.doi.org/10.1085/jgp.97.6.1227.

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Type l voltage-gated K+ channels in murine lymphocytes were studied under voltage clamp in cell-attached patches and in the whole-cell configuration. The kinetics of activation of whole-cell currents during depolarizing pulses could be fit by a single exponential after an initial delay. Deactivation upon repolarization of both macroscopic and microscopic currents was mono-exponential, except in Rb-Ringer or Cs-Ringer solution in which tail currents often displayed "hooks," wherein the current first increased or remained constant before decaying. In some cells type l currents were contaminated by a small component due to type n K+ channels, which deactivate approximately 10 times slower than type l channels. Both macroscopic and single channel currents could be dissected either kinetically or pharmacologically into these two K+ channel types. The ionic selectivity and conductance of type l channels were studied by varying the internal and external permeant ion. With 160 mM K+ in the cell, the relative permeability calculated from the reversal potential with the Goldman-Hodgkin-Katz equation was K+ (identical to 1.0) greater than Rb+ (0.76) greater than NH4+ = Cs+ (0.12) much greater than Na+ (less than 0.004). Measured 30 mV negative to the reversal potential, the relative conductance sequence was quite different: NH4+ (1.5) greater than K+ (identical to 1.0) greater than Rb+ (0.5) greater than Cs+ (0.06) much greater than Na+, Li+, TMA+ (unmeasurable). Single channel current rectification resembled that of the whole-cell instantaneous I-V relation. Anomalous mole-fraction dependence of the relative permeability PNH4/PK was observed in NH4(+)-K+ mixtures, indicating that the type l K+ channel is a multi-ion pore. Compared with other K+ channels, lymphocyte type l K+ channels are most similar to "g12" channels in myelinated nerve.

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Medovoy, David, Eduardo Perozo, and Benoît Roux. "Multi-ion free energy landscapes underscore the microscopic mechanism of ion selectivity in the KcsA channel." Biochimica et Biophysica Acta (BBA) - Biomembranes 1858, no. 7 (July 2016): 1722–32. http://dx.doi.org/10.1016/j.bbamem.2016.02.019.

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Hanao, Takafumi, Yoshiharu Uesaka, Takahiro Kawai, Yusuke Kikuchi, Naoyuki Fukumoto, and Masayoshi Nagata. "Development of Multi-channel Ion Doppler Spectroscopic System by using Fast Camera." IEEJ Transactions on Fundamentals and Materials 136, no. 3 (2016): 109–14. http://dx.doi.org/10.1541/ieejfms.136.109.

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Nagata, Masayoshi, and Tadao Uyama. "Ion Doppler Spectroscopic Measurement with a Multi-channel PMT on Spheromak Plasmas." IEEJ Transactions on Fundamentals and Materials 124, no. 2 (2004): 217–18. http://dx.doi.org/10.1541/ieejfms.124.217.

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Kim, Ilsoo, and Toby W. Allen. "Multi-Ion Mechanism of Potassium Channel Rejection of Na and Li Ions." Biophysical Journal 98, no. 3 (January 2010): 331a. http://dx.doi.org/10.1016/j.bpj.2009.12.1796.

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Sesti, F., E. Eismann, U. B. Kaupp, M. Nizzari, and V. Torre. "The multi-ion nature of the cGMP-gated channel from vertebrate rods." Journal of Physiology 487, no. 1 (August 15, 1995): 17–36. http://dx.doi.org/10.1113/jphysiol.1995.sp020858.

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SHIGAKI, KENTA. "MULTI-CHANNEL MEASUREMENTS OF LIGHT VECTOR MESONS AT PHENIX." International Journal of Modern Physics E 16, no. 07n08 (August 2007): 2154–59. http://dx.doi.org/10.1142/s0218301307007611.

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The PHENIX experiment at RHIC is uniquely suitable for systematic studies of light vector mesons, whose mass states are considered as a sensitive probe of partial chiral symmetry restoration and as a signature of deconfined partonic state of matter. Their challengingly small signal to background ratios in multi body decay channels in heavy ion collisions have been extensively attacked. Significant improvements have been recently achieved of signal extraction techniques. The final results on yields, transverse momentum spectra, and possibly mass states of light vector mesons including φ and ω are well in the near future prospects.

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Gui, Yunyun, Yihe Wang, Chiyang He, Zhouqing Tan, Lingfeng Gao, Wei Li, and Huiting Bi. "Multi-optical signal channel gold nanoclusters and their application in heavy metal ions sensing arrays." Journal of Materials Chemistry C 9, no. 8 (2021): 2833–39. http://dx.doi.org/10.1039/d0tc05160h.

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Novel multi-optical signal channel gold nanoclusters (MS-AuNCs) with CL and FL properties were designed and prepared by a one-pot method. Then the CL and FL spectra of MS-AuNCs were applied to the sensing array for heavy metal ion differentiation.

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Wan, Qian, Ji-Bin Zhuo, Xiao-Xue Wang, Cai-Xia Lin, and Yao-Feng Yuan. "A simple and highly selective 2,2-diferrocenylpropane-based multi-channel ion pair receptor for Pb2+ and HSO4−." Dalton Transactions 44, no. 12 (2015): 5790–96. http://dx.doi.org/10.1039/c4dt03862b.

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A 2,2-diferrocenylpropane-based multi-channel ion pair receptor 1 was designed and structurally characterized. It was a “naked-eye-detectable” chemosensor towards Pb²⁺ and HSO₄⁻ with excellent selectivity and sensitivity.

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Vandevender, J. Pace. "Summary (I). Experiments." Laser and Particle Beams 5, no. 3 (August 1987): 549–50. http://dx.doi.org/10.1017/s0263034600003037.

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The conference has shown some important advances toward the solution of problems required for inertial fusion. We can tentatively categorize as solved, or nearly solved, the following problems: Marx prefires, Marx jitter, gas-switch prefires, gas-switch jitter, power combination of multi-modules, high-current beam divergence (in barreltype, Applied-B/MID diodes), and preheat. In addition, there are a set of mature problems with promising solutions: pulsed power accelerator efficiency, ion sources, and the electron kinetics of an extractor ion diode. Newer problems that were addressed at the meeting but still require considerable work include: impedance control of efficient ion diodes, diagnostics for both beams and targets, the further development of target design tools and their experimental verification, targetfabrication processes to make the nearly perfect targets required for inertial fusion, channel formation and beam transport in those channels at the power levels required for fusion, and pulse-shaping.

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Formaggio, Francesco, Martina Fazzina, Raúl Estévez, Marco Caprini, and Stefano Ferroni. "Dynamic expression of homeostatic ion channels in differentiated cortical astrocytes in vitro." Pflügers Archiv - European Journal of Physiology 474, no. 2 (November 4, 2021): 243–60. http://dx.doi.org/10.1007/s00424-021-02627-x.

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AbstractThe capacity of astrocytes to adapt their biochemical and functional features upon physiological and pathological stimuli is a fundamental property at the basis of their ability to regulate the homeostasis of the central nervous system (CNS). It is well known that in primary cultured astrocytes, the expression of plasma membrane ion channels and transporters involved in homeostatic tasks does not closely reflect the pattern observed in vivo. The individuation of culture conditions that promote the expression of the ion channel array found in vivo is crucial when aiming at investigating the mechanisms underlying their dynamics upon various physiological and pathological stimuli. A chemically defined medium containing growth factors and hormones (G5) was previously shown to induce the growth, differentiation, and maturation of primary cultured astrocytes. Here we report that under these culture conditions, rat cortical astrocytes undergo robust morphological changes acquiring a multi-branched phenotype, which develops gradually during the 2-week period of culturing. The shape changes were paralleled by variations in passive membrane properties and background conductance owing to the differential temporal development of inwardly rectifying chloride (Cl−) and potassium (K+) currents. Confocal and immunoblot analyses showed that morphologically differentiated astrocytes displayed a large increase in the expression of the inward rectifier Cl− and K+ channels ClC-2 and Kir4.1, respectively, which are relevant ion channels in vivo. Finally, they exhibited a large diminution of the intermediate filaments glial fibrillary acidic protein (GFAP) and vimentin which are upregulated in reactive astrocytes in vivo. Taken together the data indicate that long-term culturing of cortical astrocytes in this chemical-defined medium promotes a quiescent functional phenotype. This culture model could aid to address the regulation of ion channel expression involved in CNS homeostasis in response to physiological and pathological challenges.

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Journal articles on the topic 'Multi-ion channel'

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