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1
Lau, Y. Y., M. Lampe, R. F. Fernsler, and B. Hui. "Current enhancement in a conducting channel." Physics of Fluids 28, no. 8 (1985): 2323. http://dx.doi.org/10.1063/1.865290.
Повний текст джерела
2
Johari, Zaharah, Nurul Ezaila Alias, and Zuriana Auzar. "Current Conduction in Dual Channel Black Phosphorene Nanoribbon Transistor." ELEKTRIKA- Journal of Electrical Engineering 17, no. 2 (August 29, 2018): 35–38. http://dx.doi.org/10.11113/elektrika.v17n2.107.
Повний текст джерелаАнотація:
Phosphorene continues to fascinate research community due to its excellent physical and electrical properties. In this paper, the feasibility study of using dual conducting channel in black phosphorene nanoribbon transistor is investigated using Atomistic simulation tool. Both electronic and transport properties are evaluated. Through simulation, it is demonstrated that the conduction behavior behave differently where the current exhibit a great deal of increment when using dual channel. The performance was superior compared to single channel and suggests that the number of conducting channel is a significant factor in improving device behavior.
3
Marom, S., D. Dagan, J. Winaver, and Y. Palti. "Brush-border membrane cation conducting channels from rat kidney proximal tubules." American Journal of Physiology-Renal Physiology 257, no. 3 (September 1, 1989): F328—F335. http://dx.doi.org/10.1152/ajprenal.1989.257.3.f328.
Повний текст джерелаАнотація:
This is a description and kinetic characterization of cation channels from rat kidney brush-border membrane vesicles and from apical membranes of proximal tubule cells in culture. Channel activity was demonstrated and characterized in both artificial phospholipid bilayers and in tissue culture. Intermediate conductance, approximately 50 pS, cation-selective channels were observed by both methods. Channels were characterized by a Na permeability (PNa)/K permeability (PK) of 1-5:1. Open-channel current-voltage curves were linear in symmetric 300 mM NaCl. In tissue culture the gating kinetics are described by two open-time constants and two closed-time constants. Channel activity was neither voltage nor Ca2+ dependent and the probability of being in the open state ranged from 0.6 to 0.95. In tissue culture experiments the channel demonstrated nonstationary gating activity. A second, 15-pS cation channel, seen in planar bilayers, demonstrated a higher selectivity for Na+ with a (PNa/PK ratio of greater than 10).
4
Olcese, Riccardo, Daniel Sigg, Ramon Latorre, Francisco Bezanilla, and Enrico Stefani. "A Conducting State with Properties of a Slow Inactivated State in a Shaker K+ Channel Mutant." Journal of General Physiology 117, no. 2 (January 29, 2001): 149–64. http://dx.doi.org/10.1085/jgp.117.2.149.
Повний текст джерелаАнотація:
In Shaker K+ channel, the amino terminus deletion Δ6-46 removes fast inactivation (N-type) unmasking a slow inactivation process. In Shaker Δ6-46 (Sh-IR) background, two additional mutations (T449V-I470C) remove slow inactivation, producing a noninactivating channel. However, despite the fact that Sh-IR-T449V-I470C mutant channels remain conductive, prolonged depolarizations (1 min, 0 mV) produce a shift of the QV curve by about −30 mV, suggesting that the channels still undergo the conformational changes typical of slow inactivation. For depolarizations longer than 50 ms, the tail currents measured during repolarization to −90 mV display a slow component that increases in amplitude as the duration of the depolarizing pulse increases. We found that the slow development of the QV shift had a counterpart in the amplitude of the slow component of the ionic tail current that is not present in Sh-IR. During long depolarizations, the time course of both the increase in the slow component of the tail current and the change in voltage dependence of the charge movement could be well fitted by exponential functions with identical time constant of 459 ms. Single channel recordings revealed that after prolonged depolarizations, the channels remain conductive for long periods after membrane repolarization. Nonstationary autocovariance analysis performed on macroscopic current in the T449V-I470C mutant confirmed that a novel open state appears with increasing prepulse depolarization time. These observations suggest that in the mutant studied, a new open state becomes progressively populated during long depolarizations (>50 ms). An appealing interpretation of these results is that the new open state of the mutant channel corresponds to a slow inactivated state of Sh-IR that became conductive.
5
Ravens, Ursula. "Atrial-selective K+ channel blockers: potential antiarrhythmic drugs in atrial fibrillation?" Canadian Journal of Physiology and Pharmacology 95, no. 11 (November 2017): 1313–18. http://dx.doi.org/10.1139/cjpp-2017-0024.
Повний текст джерелаАнотація:
In the wake of demographic change in Western countries, atrial fibrillation has reached an epidemiological scale, yet current strategies for drug treatment of the arrhythmia lack sufficient efficacy and safety. In search of novel medications, atrial-selective drugs that specifically target atrial over other cardiac functions have been developed. Here, I will address drugs acting on potassium (K+) channels that are either predominantly expressed in atria or possess electrophysiological properties distinct in atria from ventricles. These channels include the ultra-rapidly activating, delayed outward-rectifying Kv1.5 channel conducting IKur, the acetylcholine-activated inward-rectifying Kir3.1/Kir3.4 channel conducting IK,ACh, the Ca2+-activated K+ channels of small conductance (SK) conducting ISK, and the two-pore domain K+ (K2P) channels (tandem of P domains, weak inward-rectifying K+ channels (TWIK-1), TWIK-related acid-sensitive K+ channels (TASK-1 and TASK-3)) that are responsible for voltage-independent background currents ITWIK-1, ITASK-1, and ITASK-3. Direct drug effects on these channels are described and their putative value in treatment of atrial fibrillation is discussed. Although many potential drug targets have emerged in the process of unravelling details of the pathophysiological mechanisms responsible for atrial fibrillation, we do not know whether novel antiarrhythmic drugs will be more successful when modulating many targets or a single specific one. The answer to this riddle can only be solved in a clinical context.
6
Roux, Michel J., Riccardo Olcese, Ligia Toro, Francisco Bezanilla, and Enrico Stefani. "Fast Inactivation in Shaker K+ Channels." Journal of General Physiology 111, no. 5 (May 1, 1998): 625–38. http://dx.doi.org/10.1085/jgp.111.5.625.
Повний текст джерелаАнотація:
Fast inactivating Shaker H4 potassium channels and nonconducting pore mutant Shaker H4 W434F channels have been used to correlate the installation and recovery of the fast inactivation of ionic current with changes in the kinetics of gating current known as “charge immobilization” (Armstrong, C.M., and F. Bezanilla. 1977. J. Gen. Physiol. 70:567–590.). Shaker H4 W434F gating currents are very similar to those of the conducting clone recorded in potassium-free solutions. This mutant channel allows the recording of the total gating charge return, even when returning from potentials that would largely inactivate conducting channels. As the depolarizing potential increased, the OFF gating currents decay phase at −90 mV return potential changed from a single fast component to at least two components, the slower requiring ∼200 ms for a full charge return. The charge immobilization onset and the ionic current decay have an identical time course. The recoveries of gating current (Shaker H4 W434F) and ionic current (Shaker H4) in 2 mM external potassium have at least two components. Both recoveries are similar at −120 and −90 mV. In contrast, at higher potentials (−70 and −50 mV), the gating charge recovers significantly more slowly than the ionic current. A model with a single inactivated state cannot account for all our data, which strongly support the existence of “parallel” inactivated states. In this model, a fraction of the charge can be recovered upon repolarization while the channel pore is occupied by the NH2-terminus region.
7
Quinn, Kerry E., and Barbara E. Ehrlich. "Methanethiosulfonate Derivatives Inhibit Current through the Ryanodine Receptor/Channel." Journal of General Physiology 109, no. 2 (February 1, 1997): 255–64. http://dx.doi.org/10.1085/jgp.109.2.255.
Повний текст джерелаАнотація:
To identify regions of the ryanodine receptor (RyR) important for ion conduction we modified the channel with sulfhydryl-reacting compounds. After addition of methanethiosulfonate (MTS) compounds channel conductance was decreased while other channel properties, including channel regulation by ATP, caffeine, or Ca, were unaffected. The site of action was accessible to the MTS compounds from the cytoplasmic, but not the luminal, side of the channel. In addition, the hydrophilic MTS compounds were only effective when the channel was open, suggesting that the compounds covalently modify the channel from within the water-filled ion conducting pathway. The decrease in channel current amplitude occurred in a step-wise fashion and was irreversible and cumulative over time, eventually leading to the complete block of channel current. However, the time required for each consecutive modification during continuous exposure to the MTS compounds increased, suggesting that successive modification by the MTS compounds is not independent. These results are consistent with the hypothesis that the channel forms a wide vestibule on the cytoplasmic side and contains a much smaller opening on the luminal side. Furthermore, our results indicate that the MTS compounds can serve as functional markers for specific residues of the RyR to be identified in molecular studies.
8
Shcherba, A. A., N. I. Suprunovska, and M. A. Shcherba. "FEATURES OF THE FORMATION OF MULTI-CHANNEL PULSE CURRENTS AND FAST-MIGRATING ELECTRIC SPARKS IN THE LAYER OF CURRENT-CONDUCTING GRANULES OF ELECTRIC-DISCHARGE INSTALLATIONS." Tekhnichna Elektrodynamika 2022, no. 2 (March 19, 2022): 3–11. http://dx.doi.org/10.15407/techned2022.02.003.
Повний текст джерелаАнотація:
The paper reveals the electro-physical features of the formation of multi-channel pulse currents and fast-migrating electric sparks in the layer of current-conductive granules of electric-discharge installations (EDIs) with reservoir capacitors. Such features make it possible to increase many times the productivity of the electric-spark dispersion of metal granules during single discharge current of reservoir capacitors, which flows between the electrodes of EDIs. Theoretical substantiation and experimental confirmation of multi-channel spark discharges in the layer of conductive granules are presented. The influence of the capacitance and charge voltage of reservoir capacitors on the nature of transient processes in the discharge circuit of the EDIs is investigated. The dependence of the effective value of the active load resistance of the EDIs on the value of the pre-charge voltage of its reservoir capacitors and the value of its capacitances has been experimentally determined. It is proved that an increase in the averaged Q-factor of the discharge circuit with an increase in the charge voltage of the capacitor bank of EDI is caused by a decrease in the effective value of the active resistance of the layer of metal granules when spark-generating discharge currents flow through it. References 16, Figures 7.
9
Yu, Xie. "Amplifier Design on 16-Channel High-Frequency Current Drive." Advanced Materials Research 658 (January 2013): 620–25. http://dx.doi.org/10.4028/www.scientific.net/amr.658.620.
Повний текст джерелаАнотація:
According to the situation that the transistor output interface type of PLC output current is too small to meet requirements of high-speed, frequently on or off electromagnetic valve and other great current load drives, a current driver amplifier was developed which connected PLC output interface and load. Its key realization technologies include signal acquisition input, bidirectional conducting, input and output display, and designs of isolation circuit of input and output and output amplification processing circuit. The device uses bidirectional optocoupler and bidirectional LED to gather small DC current signal which does not distinguish between positive and negative polarities and achieve photoelectric isolation, controls drive load work of MOS transistor conducting and achieves current amplification through amplification driver link of emitter output, and has high frequently on-off operation, simple wiring, great drive current, strong versatility, high reliability and other characteristics.
10
Palmer, L. G., L. Antonian, and G. Frindt. "Regulation of apical K and Na channels and Na/K pumps in rat cortical collecting tubule by dietary K." Journal of General Physiology 104, no. 4 (October 1, 1994): 693–710. http://dx.doi.org/10.1085/jgp.104.4.693.
Повний текст джерелаАнотація:
The patch-clamp technique was used to study the properties and the density of conducting K and Na channels in the apical membrane of rat cortical collecting tubule. The predominant K channel observed in cell-attached patches (SK channels) had an outward single-channel conductance (with LiCl in the pipette) of 10 pS. The inward conductance (with KCl in the pipette) was 42 pS. The channel had a high open probability that increased with depolarization. Kinetic analysis indicated the presence of a single open state and two closed states. Increasing K intake by maintaining animals on a high K diet for 12-16 d increased the number of SK channels per patch by threefold (0.7-2.0/patch) over control levels. In addition, conducting Na-selective channels, which were not observed in control animals, were seen at low density (0.5/patch). These channels had properties similar to those observed when the animals were on a low Na diet, except that the mean open probability (0.84) was higher. In other experiments, the whole-cell patch clamp technique was used to measure Na channel activity (as amiloride-sensitive current, INa) and Na pump activity (as ouabain-sensitive current, Ipump). In animals on a high K diet, INa was greater than in controls but much less than in rats on a low Na diet. Ipump was greater after K loading than in controls or Na-depleted animals. These K diet-dependent effects were not accompanied by a significant increase in plasma aldosterone concentrations. To further investigate the relationship between K channel activity and mineralocorticoids, rats were maintained on a low Na diet to increase endogenous aldosterone secretion. Under these conditions, no increase in SK channel density was observed, although there was a large increase in the number of Na channels (to 2.7/patch). Aldosterone was also administered exogenously through osmotic minipumps. As with the low Na diet, there was no change in the density of conducting SK channels, although Na channel activity was induced. These results suggest that SK channels, Na channels and Na/K pumps are regulated during changes in K intake by factors other than aldosterone.
11
Grossmann, J. M., P. F. Ottinger, and R. J. Mason. "Current channel migration and magnetic field penetration in a perfectly conducting plasma with emitting, conducting boundaries." Journal of Applied Physics 66, no. 6 (September 15, 1989): 2307–14. http://dx.doi.org/10.1063/1.344287.
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12
Tyutyaev, Pavel, та Stephan Grissmer. "Characterization of the σ-Pore in Mutant hKv1.3 Potassium Channels". Cellular Physiology and Biochemistry 46, № 3 (2018): 1112–21. http://dx.doi.org/10.1159/000488840.
Повний текст джерелаАнотація:
Background/Aims: The replacement of the amino acid valine at position 388 (Shaker position 438) in hKv1.3 channels or at the homologue position 370 in hKv1.2 channels resulted in a channel with two different ion conducting pathways: One pathway was the central, potassium-selective α-pore, that was sensitive to block by peptide toxins (CTX or KTX in the hKv1.3_V388C channel and CTX or MTX in the hKv1.2_V370C channel). The other pathway (σ-pore) was behind the central α-pore creating an inward current at potentials more negative than -100 mV, a potential range where the central α-pore was closed. In addition, current through the σ-pore could not be reduced by CTX, KTX or MTX in the hKv1.3_V388C or the hKv1.2_V370C channel, respectively. Methods: For a more detailed characterization of the σ-pore, we created a trimer consisting of three hKv1.3_V388C α-subunits linked together and characterized current through this trimeric hKv1.3_V388C channel. Additionally, we determined which amino acids line the σ-pore in the tetrameric hKv1.3_V388C channel by replacing single amino acids in the tetrameric hKv1.3_V388C mutant channel that could be involved in σ-pore formation. Results: Overexpression of the trimeric hKv1.3_V388C channel in COS-7 cells yielded typical σ-pore currents at potentials more negative than -100 mV similar to what was observed for the tetrameric hKv1.3_V388C channel. Electrophysiological properties of the trimeric and tetrameric channel were similar: currents could be observed at potentials more negative than -100 mV, were not carried by protons or chloride ions, and could not be reduced by peptide toxins (CTX, MTX) or TEA. The σ-pore was mostly permeable to Na+ and Li+. In addition, in our site-directed mutagenesis experiments, we created a number of new double mutant channels in the tetrameric hKv1.3_V388C background channel. Two of these tetrameric double mutant channels (hKv1.3_V388C_T392Y and hKv1.3_V388C_Y395W) did not show currents through the σ-pore. Conclusions: From our experiments with the trimeric hKv1.3_V388C channel we conclude that the σ-pore exists in hKv1.3_V388C channels independently of the α-pore. From our site-directed mutagenesis experiments in the tetrameric hKv1.3_V388C channel we conclude that amino acid position 392 and 395 (Shaker position 442 and 445) line the σ-pore.
13
Benzinger, G. Richard, Xiao-Ming Xia та Christopher J. Lingle. "Direct Observation of a Preinactivated, Open State in BK Channels with β2 Subunits". Journal of General Physiology 127, № 2 (17 січня 2006): 119–31. http://dx.doi.org/10.1085/jgp.200509425.
Повний текст джерелаАнотація:
Proteins arising from the Slo family assemble into homotetramers to form functional large-conductance, Ca2+- and voltage-activated K+ channels, or BK channels. These channels are also found in association with accessory β subunits, which modulate several aspects of channel gating and expression. Coexpression with either of two such subunits, β2 or β3b, confers time-dependent inactivation onto BK currents. mSlo1+β3b channels display inactivation that is very rapid but incomplete. Previous studies involving macroscopic recordings from these channels have argued for the existence of a second, short-lived conducting state in rapid equilibrium with the nonconducting, inactivated conformation. This state has been termed “pre-inactivated,” or O*. β2-mediated inactivation, in contrast, occurs more slowly but is virtually complete at steady state. Here we demonstrate, using both macroscopic and single channel current recordings, that a preinactivated state is also a property of mSlo1+β2 channels. Detection of this state is enhanced by a mutation (W4E) within the initial β2 NH2-terminal segment critical for inactivation. This mutation increases the rate of recovery to the preinactivated open state, yielding macroscopic inactivation properties qualitatively more similar to those of β3b. Furthermore, short-lived openings corresponding to entry into the preinactivated state can be observed directly with single-channel recording. By examining the initial openings after depolarization of a channel containing β2-W4E, we show that channels can arrive directly at the preinactivated state without passing through the usual long-lived open conformation. This final result suggests that channel opening and inactivation are at least partly separable in this channel. Mechanistically, the preinactivated and inactivated conformations may correspond to binding of the β subunit NH2 terminus in the vicinity of the cytoplasmic pore mouth, followed by definitive movement of the NH2 terminus into a position of occlusion within the ion-conducting pathway.
14
Javor, V. "Modeling of Lightning Strokes Using Two-Peaked Channel-Base Currents." International Journal of Antennas and Propagation 2012 (2012): 1–7. http://dx.doi.org/10.1155/2012/318417.
Повний текст джерелаАнотація:
Lightning electromagnetic field is obtained by using “engineering” models of lightning return strokes and new channel-base current functions and the results are presented in this paper. Experimentally measured channel-base currents are approximated not only with functions having two-peaked waveshapes but also with the one-peaked function so as usually used in the literature. These functions are simple to be applied in any “engineering” or electromagnetic model as well. For the three “engineering” models: transmission line model (without the peak current decay), transmission line model with linear decay, and transmission line model with exponential decay with height, the comparison of electric and magnetic field components at different distances from the lightning channel-base is presented in the case of a perfectly conducting ground. Different heights of lightning channels are also considered. These results enable analysis of advantages/shortages of the used return stroke models according to the electromagnetic field features to be achieved, as obtained by measurements.
15
Prütting, Sylvia, and Stephan Grissmer. "A Novel Current Pathway Parallel to the Central Pore in a Mutant Voltage-gated Potassium Channel." Journal of Biological Chemistry 286, no. 22 (April 15, 2011): 20031–42. http://dx.doi.org/10.1074/jbc.m110.185405.
Повний текст джерелаАнотація:
Voltage-gated potassium channels are proteins composed of four subunits consisting of six membrane-spanning segments S1–S6, with S4 as the voltage sensor. The region between S5 and S6 forms the potassium-selective ion-conducting central α-pore. Recent studies showed that mutations in the voltage sensor of the Shaker channel could disclose another ion permeation pathway through the voltage-sensing domain (S1–S4) of the channel, the ω-pore. In our studies we used the voltage-gated hKv1.3 channel, and the insertion of a cysteine at position V388C (Shaker position 438) generated a current through the α-pore in high potassium outside and an inward current at hyperpolarizing potentials carried by different cations like Na+, Li+, Cs+, and NH4+. The observed inward current looked similar to the ω-current described for the R1C/S Shaker mutant channel and was not affected by some pore blockers like charybdotoxin and tetraethylammonium but was inhibited by a phenylalkylamine blocker (verapamil) that acts from the intracellular side. Therefore, we hypothesize that the hKv1.3_V388C mutation in the P-region generated a channel with two ion-conducting pathways. One, the α-pore allowing K+ flux in the presence of K+, and the second pathway, the σ-pore, functionally similar but physically distinct from the ω-pathway. The entry of this new pathway (σ-pore) is presumably located at the backside of Y395 (Shaker position 445), proceeds parallel to the α-pore in the S6–S6 interface gap, ending between S5 and S6 at the intracellular side of one α-subunit, and is blocked by verapamil.
16
Gerasimov, Alexander, and Alexander Kirpichnikov. "Quasi-equilibrium channel model of an constant current arc." Thermal Science 7, no. 1 (2003): 101–8. http://dx.doi.org/10.2298/tsci0301101g.
Повний текст джерелаАнотація:
The rather simple method of calculation of electronic and gas temperature in the channel of arc of plasma generator is offered. This method is based on self-consistent two-temperature channel model of an electric arc. The method proposed enables to obtain radial allocation of gas and electronic temperatures in a non-conducting zone of an constant current arc, for prescribed parameters of discharge (current intensity and power of the discharge), with enough good precision. The results obtained can be used in model and engineering calculations to estimate gas and electronic temperatures in the channel of an arc plasma generator.
17
Spanjers, G. G., E. J. Yadlowsky, R. C. Hazelton, and J. J. Moschella. "Investigation of current channel migration in a conducting plasma between planar electrodes." Journal of Applied Physics 79, no. 5 (March 1996): 2229–36. http://dx.doi.org/10.1063/1.361106.
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18
MARSH, Derek. "Peptide models for membrane channels." Biochemical Journal 315, no. 2 (April 15, 1996): 345–61. http://dx.doi.org/10.1042/bj3150345.
Повний текст джерелаАнотація:
Peptides may be synthesized with sequences corresponding to putative transmembrane domains and/or pore-lining regions that are deduced from the primary structures of ion channel proteins. These can then be incorporated into lipid bilayer membranes for structural and functional studies. In addition to the ability to invoke ion channel activity, critical issues are the secondary structures adopted and the mode of assembly of these short transmembrane peptides in the reconstituted systems. The present review concentrates on results obtained with peptides from ligand-gated and voltage-gated ion channels, as well as proton-conducting channels. These are considered within the context of current molecular models and the limited data available on the structure of native ion channels and natural channel-forming peptides.
19
Song, Woochul, Chao Lang, Yue-xiao Shen, and Manish Kumar. "Design Considerations for Artificial Water Channel–Based Membranes." Annual Review of Materials Research 48, no. 1 (July 2018): 57–82. http://dx.doi.org/10.1146/annurev-matsci-070317-124544.
Повний текст джерелаАнотація:
Aquaporins (AQPs) are naturally occurring water channel proteins. They can facilitate water molecule translocation across cellular membranes with exceptional selectivity and high permeability that are unmatched in synthetic membrane systems. These unique properties of AQPs have led to their use as functional elements in membranes in recent years. However, the intricate nature of AQPs and concerns regarding their stability and processability have encouraged researchers to develop synthetic channels that mimic the structure and properties of AQPs and other biological water-conducting channels. These channels have been termed artificial water channels. This article reviews current progress and provides a historical perspective as well as an outlook toward developing scalable membranes based on artificial water channels.
20
Haynes, L. W. "Block of the cyclic GMP-gated channel of vertebrate rod and cone photoreceptors by l-cis-diltiazem." Journal of General Physiology 100, no. 5 (November 1, 1992): 783–801. http://dx.doi.org/10.1085/jgp.100.5.783.
Повний текст джерелаАнотація:
Inside-out patches were excised from catfish rod or cone outer segments. Single channel and macroscopic currents were recorded from GMP-gated channels activated by 1 mM cGMP in low divalent buffered saline. Currents were blocked by the application of micromolar concentrations of l-cis-diltiazem to the cytoplasmic side of the patch. The concentration dependence of block indicated that a single molecule was sufficient to block a channel and that all channels were susceptible to block. The dissociation constant for the rod channel was an order of magnitude smaller than for the cone channel, but the voltage dependence of block was nearly identical. The macroscopic current-voltage relation in the presence of blocker was inwardly rectifying and superficially resembled voltage-dependent block by an impermeant blocker occluding the ion-conducting pore of the channel. Block by diltiazem acting from the extracellular side of the channel was investigated by including 5 microM diltiazem in the recording pipette solution. The macroscopic current-voltage relation again showed inward rectification, inconsistent with the idea that diltiazem acts by occluding the pore at the external side. The kinetics of block by diltiazem applied to the intra- and extracellular side were measured in cone patches containing only a single channel. The unbinding rates were similar in both cases, suggesting a single binding site. Differences in the binding rate were consistent with greater accessibility to the binding site from the cytoplasmic side. Block from the cytoplasmic side was independent of pH, suggesting that the state of ionization of diltiazem was not related to its ability to block the channel in a voltage-dependent fashion. These observations are inconsistent with a pore-occluding blocker, but could be explained if the hydrophobic portion of diltiazem partitioned into the hydrophobic core of the channel protein, perhaps altering the gating of the channel.
21
Zheng, Jie, and Fred J. Sigworth. "Intermediate Conductances during Deactivation of Heteromultimeric Shaker Potassium Channels." Journal of General Physiology 112, no. 4 (October 1, 1998): 457–74. http://dx.doi.org/10.1085/jgp.112.4.457.
Повний текст джерелаАнотація:
A previous study of the T442S mutant Shaker channel revealed activation-coupled subconductance levels that apparently represent kinetic intermediates in channel activation (Zheng, J., and F.J. Sigworth. 1997. J. Gen. Physiol. 110:101–117). We have now extended the study to heteromultimeric channels consisting of various numbers of mutant subunits as well as channels without mutant subunits, all in the background of a chimeric Shaker channel having increased conductance. It has been found that activation-coupled sublevels exist in all these channel types, and are traversed in at least 80% of all deactivation time courses. In symmetric K+ solutions, the currents in the two sublevels have a linear voltage dependence, being 23–44% and 54–70% of the fully open conductance. Sublevels in different channel types share similar voltage dependence of the mean lifetime and similar ion selectivity properties. However, the mean lifetime of each current level depends approximately geometrically on the number of mutant subunits in the channel, becoming shorter in channels having fewer mutant subunits. Each mutant subunit appears to stabilize all of the conducting states by ∼0.5 kcal/mol. Consistent with previous results in the mutant channel, sublevels in channels with two or no mutant subunits also showed ion selectivities that differ from that of the fully open level, having relatively higher K+ than Rb+ conductances. A model is presented in which Shaker channels have two coupled activation gates, one associated with the selectivity filter and a second associated with the S6 helix bundle.
22
KIM, Konstantin I., Konstantin K. KIM, Alexander Yu PANYCHEV, and Lyudmila S. BLAZHKO. "Electromagnetic processes in an anisotropically electrically conducting liquid in a running magnetic field." BULLETIN OF SCIENTIFIC RESEARCH RESULTS, no. 3 (September 30, 2021): 7–23. http://dx.doi.org/10.20295/2223-9987-2021-3-7-23.
Повний текст джерелаАнотація:
Objective: Purpose is the study electromagnetic processes in an electrically conducting liquid (with anisotropic conductivity) flowing in the channel of an MHD-alternator under the acting of a running magnetic field. Methods: We used Maxwell's equations to describe the electromagnetic processes. Galerkin method is used to determine the current functions. Results: For the case of small values of the magnetic Reynolds number the equations for the induced field and currents in an electrical conducting liquid are given in the form of converging power series. It is shown that for a sufficiently accurate determination of the current functions it is necessary to take into account the first three terms of the series. The first two terms of the other series must be taken into account to determi-nate the solution for the induced field. It is revealed that the induced currents in an electrically conducting liquid consist of currents of zero, main and double frequencies. The currents of zero and double frequencies play a negative role since they lead to an increase in joule losses and the for-mation of forces. These forces do not make the useful work. To reduce them the side walls of the channel should be conductive. We established that the anisotropy of the electrical conductivity of the liquid causes a decrease the currents of the main frequency. Practical importance: The magnet-ic Reynolds number significantly affects the field distribution in a liquid metal. The field of the main frequency increases with its increase and the fields of zero and double frequency become smaller. At the small values of Reynolds number the Hall effect is stronger and the field distribution is less symmetrical. At large values the field distribution is symmetrized due to a decrease in the zero and doub¬le frequency fields.
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Xiao, Xue Jiao, and Chang Nyung Kim. "Computational Analysis of a Magnetohydrodynamic Flow in an Electrically Conducting Hairpin Duct." Applied Mechanics and Materials 527 (February 2014): 43–48. http://dx.doi.org/10.4028/www.scientific.net/amm.527.43.
Повний текст джерелаАнотація:
This numerical study examines a three-dimensional liquid-metal magnetohydrodynamic flow in a hairpin-shaped electrically-conducting duct with a square cross-section under a uniform magnetic field applied perpendicular to the flow plane. Predicted is detailed information on fluid velocity, pressure, current, and electric potential in the magnetohydrodynamic duct flow. Higher velocities are observed in the side layers in the inflow and outflow channels, yielding M-shaped velocity profiles. More specifically, in the present study the axial velocity in the side layer near the partitioning wall is higher than that near the outer walls because of the current features therein. In the turning segment, a large velocity recirculation is observed at the entrance of the outflow channel caused by the flow separation, yielding complicated distributions of the electric potential and current therein. The pressure almost linearly decreases along the main flow direction, except for in the turning segment.
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Serebrova, N., and V. Lavrinovsky. "Adaptive control system for multi-channel semi-conducting current stabilizer with signal tuning." TRANSACTIONS OF THE KRYLOV STATE RESEARCH CENTRE S-I, no. 2 (September 2, 2019): 212–18. http://dx.doi.org/10.24937/2542-2324-2019-2-s-i-212-218.
Повний текст джерела
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Hong, En, Fatma Gurel Kazanci, and Astrid A. Prinz. "Different Roles of Related Currents in Fast and Slow Spiking of Model Neurons From Two Phyla." Journal of Neurophysiology 100, no. 4 (October 2008): 2048–61. http://dx.doi.org/10.1152/jn.90567.2008.
Повний текст джерелаАнотація:
Neuronal activity arises from the interplay of membrane and synaptic currents. Although many channel proteins conducting these currents are phylogenetically conserved, channels of the same type in different animals can have different voltage dependencies and dynamics. What does this mean for our ability to derive rules about the role of different types of ion channels in neuronal activity? Can results about the role of a particular channel type in a particular type of neuron be generalized to other neuron types? We compare spiking model neurons in two databases constructed by exploring the maximal conductance spaces of two models. The first is a model of crustacean stomatogastric neurons, and the second is a model of rodent thalamocortical neurons, but both models contain similar types of membrane currents. Spiking neurons in both databases show distinct fast and slow subpopulations, but our analysis reveals that related currents play different roles in fast and slow spiking in the stomatogastric versus thalamocortical neurons. This analysis involved conductance-space visualization and comparison of voltage traces, current traces, and frequency-current relationships from all spiker subpopulations. Our results are consistent with previous work indicating that the role a membrane current plays in shaping a neuron's behavior depends on the voltage dependence and dynamics of that current and may be different in different neuron types depending on the properties of other currents it is interacting with. Conclusions about the function of a type of membrane current based on experiments or simulations in one type of neuron may therefore not generalize to other neuron types.
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Andalib, Payam, Michael J. Wood, and Stephen J. Korn. "Control of Outer Vestibule Dynamics and Current Magnitude in the Kv2.1 Potassium Channel." Journal of General Physiology 120, no. 5 (October 29, 2002): 739–55. http://dx.doi.org/10.1085/jgp.20028639.
Повний текст джерелаАнотація:
In Kv2.1 potassium channels, changes in external [K+] modulate current magnitude as a result of a K+-dependent interconversion between two outer vestibule conformations. Previous evidence indicated that outer vestibule conformation (and thus current magnitude) is regulated by the occupancy of a selectivity filter binding site by K+. In this paper, we used the change in current magnitude as an assay to study how the interconversion between outer vestibule conformations is controlled. With 100 mM internal K+, rapid elevation of external [K+] from 0 to 10 mM while channels were activated produced no change in current magnitude (outer vestibule conformation did not change). When channels were subsequently closed and reopened in the presence of elevated [K+], current magnitude was increased (outer vestibule conformation had changed). When channels were activated in the presence of low internal [K+], or when K+ flow into conducting channels was transiently interrupted by an internal channel blocker, increasing external [K+] during activation did increase current magnitude (channel conformation did change). These data indicate that, when channels are in the activated state under physiological conditions, the outer vestibule conformation remains fixed despite changes in external [K+]. In contrast, when channel occupancy is lowered, (by channel closing, an internal blocker or low internal [K+]), the outer vestibule can interconvert between the two conformations. We discuss evidence that the ability of the outer vestibule conformation to change is regulated by the occupancy of a nonselectivity filter site by K+. Independent of the outer vestibule-based potentiation mechanism, Kv2.1 was remarkably insensitive to K+-dependent processes that influence current magnitude (current magnitude changed by <7% at membrane potentials between −20 and 30 mV). Replacement of two outer vestibule lysines in Kv2.1 by smaller neutral amino acids made current magnitude dramatically more sensitive to the reduction in K+ driving force (current magnitude changed by as much as 40%). When combined, these outer vestibule properties (fixed conformation during activation and the presence of lysines) all but prevent variation in Kv2.1 current magnitude when [K+] changes during activation. Moreover, the insensitivity of Kv2.1 current magnitude to changes in K+ driving force promotes a more uniform modulation of current over a wide range of membrane potentials by the K+-dependent regulation of outer vestibule conformation.
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Lai, Chun Hung, Chia Hung Chen, and Chih Yi Liu. "Resistive Switching and Current Conduction for Thermally Grown NiO Thin Film." Materials Science Forum 687 (June 2011): 163–66. http://dx.doi.org/10.4028/www.scientific.net/msf.687.163.
Повний текст джерелаАнотація:
The unipolar resistive switching (URS) properties were investigated for NiO thin film prepared by thermal oxidation of the deposited Ni layer on Pt substrate. The turn-on voltage (Vset) shows apparent variation, at which switching from a high-resistance state (off) to a low-resistance state (on) occurs. The formation and rupture of a conducting channel are commonly proposed to explain the bistable conduction states, so called the filament model. The Vset polarity and instability are discussed in the light of the filament model and the results agree with the p-type carriers known in NiO film. Current-voltage data of the on-state conduction in full-log scale follow the ohmic behavior and the temperature dependence shows the relatively stable essence. The off-state current displays space-charge limited (SCL) relation at higher field and reveals a positive temperature dependence. The dominance of the off-state conduction for resistance swtich effect is emphasized and analyzed using the impedance spectroscopy.
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Wakamori, Minoru, Mark Strobeck, Tetsuhiro Niidome, Tetsuyuki Teramoto, Keiji Imoto, and Yasuo Mori. "Functional Characterization of Ion Permeation Pathway in the N-Type Ca2+ Channel." Journal of Neurophysiology 79, no. 2 (February 1, 1998): 622–34. http://dx.doi.org/10.1152/jn.1998.79.2.622.
Повний текст джерелаАнотація:
Wakamori, Minoru, Mark Strobeck, Tetsuhiro Niidome, Tetsuyuki Teramoto, Keiji Imoto, and Yasuo Mori. Functional characterization of ion permeation pathway in the N-type Ca2+ channel. J. Neurophysiol. 79: 622–634, 1998. Multiple types of high-voltage-activated Ca2+ channels, including L-, N-, P-, Q- and R-types have been distinguished from each other mainly employing pharmacological agents that selectively block particular types of Ca2+ channels. Except for the dihydropyridine-sensitive L-type Ca2+ channels, electrophysiological characterization has yet to be conducted thoroughly enough to biophysically distinguish the remaining Ca2+ channel types. In particular, the ion permeation properties of N-type Ca2+ channels have not been clarified, although the kinetic properties of both the L- and N-type Ca2+ channels are relatively well described. To establish ion conducting properties of the N-type Ca2+ channel, we examined a homogeneous population of recombinant N-type Ca2+ channels expressed in baby hamster kidney cells, using a conventional whole cell patch-clamp technique. The recombinant N-type Ca2+ channel, composed of the α1B, α2a, and β1a subunits, displayed high-voltage-activated Ba2+ currents elicited by a test pulse more positive than −30 mV, and were strongly blocked by the N-type channel blocker ω-conotoxin-GVIA. In the presence of 110 mM Ba2+, the unitary current showed a slope conductance of 18.2 pS, characteristic of N-type channels. Ca2+ and Sr2+ resulted in smaller ion fluxes than Ba2+, with the ratio 1.0:0.72:0.75 of maximum conductance in current-voltage relationships of Ba2+, Ca2+, and Sr2+ currents, respectively. In mixtures of Ba2+ and Ca2+, where the Ca2+ concentration was steadily increased in place of Ba2+, with the total concentration of Ba2+ and Ca2+ held constant at 3 mM, the current amplitude went through a clear minimum when 20% of the external Ba2+ was replaced by Ca+2. This anomalous mole fraction effect suggests an ion-binding site where two or more permeant ions can sit simultaneously. By using an external solution containing 110 mM Na+ without polyvalent cations, inward Na+ currents were evoked by test potentials more positive than −50 mV. These currents were activated and inactivated in a kinetic manner similar to that of Ba2+ currents. Application of inorganic Ca2+ antagonists blocked Ba2+ currents through N-type channels in a concentration-dependent manner. The rank order of inhibition was La3+ ≥ Cd2+ ≫ Zn2+ > Ni2+ ≥ Co2+. When a short strong depolarization was applied before test pulses of moderate depolarizing potentials, relief from channel blockade by La3+ and Cd2+ and subsequent channel reblocking was observed. The measured rate (2 × 108 M−1 s−1) of reblocking approached the diffusion-controlled limit. These results suggest that N-type Ca2+ channels share general features of a high affinity ion-binding site with the L-type Ca2+ channel, and that this site is easily accessible from the outside of the channel pore.
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Seth, G. S., S. Sarkar, and O. D. Makinde. "Combined Free and Forced Convection Couette-Hartmann Flow in a Rotating Channel with Arbitrary Conducting Walls and Hall Effects." Journal of Mechanics 32, no. 5 (August 17, 2016): 613–29. http://dx.doi.org/10.1017/jmech.2016.70.
Повний текст джерелаАнотація:
AbstractCombined free and forced convection Couette-Hartmann flow of a viscous, incompressible and electrically conducting fluid in rotating channel with arbitrary conducting walls in the presence of Hall current is investigated. Boundary conditions for magnetic field and expressions for shear stresses at the walls and mass flow rate are derived. Asymptotic analysis of solution for large values of rotation and magnetic parameters is performed to highlight nature of modified Ekmann and Hartmann boundary layers. Numerical solution of non-linear energy equation and rate of heat transfer at the walls are computed with the help of MATHEMATICA. It is found that velocity depends on wall conductance ratio of moving wall and on the sum of wall conductance ratios of both the walls of channel. There arises reverse flow in the secondary flow direction near central region of the channel due to thermal buoyancy force. Thermal buoyancy force, rotation, Hall current and wall conductance ratios resist primary fluid velocity whereas thermal buoyancy force and Hall current favor secondary fluid velocity in the region near lower wall of the channel. Magnetic field favors both the primary and secondary fluid velocities in the region near lower wall of the channel.
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ZHANG, Zongming, Yufang TANG, and Michael Xi ZHU. "Increased inwardly rectifying potassium currents in HEK-293 cells expressing murine transient receptor potential 4." Biochemical Journal 354, no. 3 (March 8, 2001): 717–25. http://dx.doi.org/10.1042/bj3540717.
Повний текст джерелаАнотація:
Drosophila transient receptor potential (Trp) and its mammalian homologues are postulated to form capacitative Ca2+ entry or store-operated channels. Here we show that expression of murine Trp4 in HEK 293 cells also leads to an increase in inwardly rectifying K+ currents. No similar increase was found in cell lines expressing Trp1, Trp3 or Trp6. Consistent with typical characteristics of inward rectifiers, the K+ currents in Trp4-expressing cells were blocked by low millimolar concentrations of Cs+ and Ba2+, but not by 1.2mM Ca2+, and were only slightly inhibited by 5mM tetraethylammonium. Single channel recordings of excised inside-out patches revealed the presence of two conducting states of 51pS and 94pS in Trp4-expressing cells. The outward current in the excised patches was blocked by 1mM spermine, but not by 1mM Mg2+. How Trp4 expression causes the increase in the K+ currents is not known. We propose that Trp4 either participates in the formation of a novel K+ channel or up-regulates the expression or activity of endogenous inwardly rectifying K+ channels.
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Merlin, Didier, Gang Yue, Wayne I. Lencer, Michael E. Selsted, and James L. Madara. "Cryptdin-3 induces novel apical conductance(s) in Cl− secretory, including cystic fibrosis, epithelia." American Journal of Physiology-Cell Physiology 280, no. 2 (February 1, 2001): C296—C302. http://dx.doi.org/10.1152/ajpcell.2001.280.2.c296.
Повний текст джерелаАнотація:
Opening of anion-conductive pathways in apical membranes of secretory cells lining mucosal surfaces is a critical step in salt and water secretion and, thus, hydration of sites including airway and intestine. In intestine, Paneth cells are positioned at the base of the secretory gland (crypt) and release defensin peptide, in mice termed cryptdins, into the crypt lumen. Because at least some defensins have been shown to form anion-conductive channels in phospholipid bilayers, we tested whether these endogenous antimicrobial peptides could act as soluble inducers of channel-like activity when applied to apical membranes. To directly evaluate the possibility of cryptdin-3-mediated apical anion conductance ( G ap), we have utilized amphotericin B to selectively permeabilize basolateral membranes of electrically tight monolayers of polarized human intestinal secretory epithelia (T84 cells), thus isolating the apical membrane for study. Cryptdin-3 induces G ap that is voltage independent (Δ G ap = 1.90 ± 0.60 mS/cm2) and exhibits ion selectivity contrasting to that elicited by forskolin or thapsigargin (for cryptdin-3, Cl− = gluconate; for forskolin and thapsigargin, Cl− ≫ gluconate). We cannot exclude the possibility that the macroscopic current induced by cryptdin could be the sum of cation and Cl− currents. Cryptdin-3 induces a current in basolaterally permeabilized epithelial monolayers derived from airway cells harboring the ΔF508 mutation of cystic fibrosis (CF; Δ G ap = 0.80 ± 0.06 mS/cm2), demonstrating that cryptdin-3 restores anion secretion in CF cells; this occurs independently of the CF transmembrane conductance regulator channel. These results support the idea that cryptdin-3 may associate with apical membranes of Cl−-secreting epithelia and self-assemble into conducting channels capable of mediating a physiological response.
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Keramidas, Angelo, та Neil L. Harrison. "The activation mechanism of α1β2γ2S and α3β3γ2S GABAA receptors". Journal of General Physiology 135, № 1 (28 грудня 2009): 59–75. http://dx.doi.org/10.1085/jgp.200910317.
Повний текст джерелаАнотація:
The α1β2γ2 and α3β3γ2 are two isoforms of γ-aminobutyric acid type A (GABAA) receptor that are widely distributed in the brain. Both are found at synapses, for example in the thalamus, where they mediate distinctly different inhibitory postsynaptic current profiles, particularly with respect to decay time. The two isoforms were expressed in HEK293 cells, and single-channel activity was recorded from outside-out patches. The kinetic characteristics of both isoforms were investigated by analyzing single-channel currents over a wide range of GABA concentrations. α1β2γ2 channels exhibited briefer active periods than α3β3γ2 channels over the entire range of agonist concentrations and had lower intraburst open probabilities at subsaturating concentrations. Activation mechanisms were constructed by fitting postulated schemes to data recorded at saturating and subsaturating GABA concentrations simultaneously. Reaction mechanisms were ranked according to log-likelihood values and how accurately they simulated ensemble currents. The highest ranked mechanism for both channels consisted of two sequential binding steps, followed by three conducting and three nonconducting configurations. The equilibrium dissociation constant for GABA at α3β3γ2 channels was ∼2.6 µM compared with ∼19 µM for α1β2γ2 channels, suggesting that GABA binds to the α3β3γ2 channels with higher affinity. A notable feature of the mechanism was that two consecutive doubly liganded shut states preceded all three open configurations. The lifetime of the third shut state was briefer for the α3β3γ2 channels. The longer active periods, higher affinity, and preference for conducting states are consistent with the slower decay of inhibitory currents at synapses that contain α3β3γ2 channels. The reaction mechanism we describe here may also be appropriate for the analysis of other types of GABAA receptors and provides a framework for rational investigation of the kinetic effects of a variety of therapeutic agents that activate or modulate GABAA receptors and hence influence synaptic and extrasynaptic inhibition in the central nervous system.
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Aleshin, A. N., and O. A. Ruban. "Temperature-Frequency Study of Germanium Selenide Memristors with a Self-Directed Current-Conducting Channel." Russian Microelectronics 51, no. 2 (April 2022): 59–67. http://dx.doi.org/10.1134/s1063739722020020.
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Patil, Rahul. "Design of Canal by Closing out Debits of Current Canal System." International Journal for Research in Applied Science and Engineering Technology 9, no. VI (June 25, 2021): 2231–37. http://dx.doi.org/10.22214/ijraset.2021.35463.
Повний текст джерелаАнотація:
Canals are natural streams channels, or manmade streams, for water movement, or to support water movement, or to support water transport vehicles. Fundamental capacity of waterway is to convey water from water assets for irrigation or domestic utilization of water. The whole water movement framework for water system, containing the fundamental channel, branch waterways, major and minor distributaries. Water is a valuable asset. It is needed by human in doing distinctive day by day exercises. This valuable asset while going through the canal is lost from the channels through leakage from the sides and lower part of the canals and by evaporation from the top water surface of the canals. This project aims at modelling a canal section using HEC-RAS conducting flow analysis such that there is no silting and scouring in the canal. HEC-RAS is a computer program that help model the hydraulics of water flow through natural rivers and artificial or natural channels. The objective is to estimate evaporation and seepage losses and suggest necessary remedies in order to avoid these water debits from the canals.
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Gray, Daniel A., Gustavo Frindt, and Lawrence G. Palmer. "Quantification of K+ secretion through apical low-conductance K channels in the CCD." American Journal of Physiology-Renal Physiology 289, no. 1 (July 2005): F117—F126. http://dx.doi.org/10.1152/ajprenal.00471.2004.
Повний текст джерелаАнотація:
Outward and inward currents through single small-conductance K+ (SK) channels were measured in cell-attached patches of the apical membrane of principal cells of the rat cortical collecting duct (CCD). Currents showed mild inward rectification with high [K+] in the pipette (Kp+), which decreased as Kp+ was lowered. Inward conductances had a hyperbolic dependence on Kp+ with half-maximal conductance at ∼20 mM. Outward conductances, measured near the reversal potential, also increased with Kp+ from 15 pS (Kp+ = 0) to 50 pS (Kp+ = 134 mM). SK channel density was measured as the number of conducting channels per patch in cell-attached patches. As reported previously, channel density increased when animals were on a high-K diet for 7 days. Addition of 8-cpt-cAMP to the bath at least 5 min before making a seal increased SK channel density to an even greater extent, although this increase was not additive with the effect of a high-K diet. In contrast, increases in Na channel activity, assessed as the whole cell amiloride-sensitive current, due to K loading and 8-cpt-cAMP treatment were additive. Single-channel conductances and channel densities were used as inputs to a simple mathematical model of the CCD to predict rates of transepithelial Na+ and K+ transport as a function of apical Na+ permeability and K+ conductance, basolateral pump rates and K+ conductance, and the paracellular conductance. With measured values for these parameters, the model predicted transport rates that were in good agreement with values measured in isolated, perfused tubules. The number and properties of SK channels account for K+ transport by the CCD under all physiological conditions tested.
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Wang, Zhuren, Nathan C. Wong, Yvonne Cheng, Steven J. Kehl, and David Fedida. "Control of voltage-gated K+ channel permeability to NMDG+ by a residue at the outer pore." Journal of General Physiology 133, no. 4 (March 30, 2009): 361–74. http://dx.doi.org/10.1085/jgp.200810139.
Повний текст джерелаАнотація:
Crystal structures of potassium (K+) channels reveal that the selectivity filter, the narrow portion of the pore, is only ∼3-Å wide and buttressed from behind, so that its ability to expand is highly constrained, and the permeation of molecules larger than Rb+ (2.96 Å in diameter) is prevented. N-methyl-d-glucamine (NMDG+), an organic monovalent cation, is thought to be a blocker of Kv channels, as it is much larger (∼7.3 Å in mean diameter) than K+ (2.66 Å in diameter). However, in the absence of K+, significant NMDG+ currents could be recorded from human embryonic kidney cells expressing Kv3.1 or Kv3.2b channels and Kv1.5 R487Y/V, but not wild-type channels. Inward currents were much larger than outward currents due to the presence of intracellular Mg2+ (1 mM), which blocked the outward NMDG+ current, resulting in a strong inward rectification. The NMDG+ current was inhibited by extracellular 4-aminopyridine (5 mM) or tetraethylammonium (10 mM), and largely eliminated in Kv3.2b by an S6 mutation that prevents the channel from opening (P468W) and by a pore helix mutation in Kv1.5 R487Y (W472F) that inactivates the channel at rest. These data indicate that NMDG+ passes through the open ion-conducting pore and suggest a very flexible nature of the selectivity filter itself. 0.3 or 1 mM K+ added to the external NMDG+ solution positively shifted the reversal potential by ∼16 or 31 mV, respectively, giving a permeability ratio for K+ over NMDG+ (PK+/PNMDG+) of ∼240. Reversal potential shifts in mixtures of K+ and NMDG+ are in accordance with PK+/PNMDG+, indicating that the ions compete for permeation and suggesting that NMDG+ passes through the open state. Comparison of the outer pore regions of Kv3 and Kv1.5 channels identified an Arg residue in Kv1.5 that is replaced by a Tyr in Kv3 channels. Substituting R with Y or V allowed Kv1.5 channels to conduct NMDG+, suggesting a regulation by this outer pore residue of Kv channel flexibility and, as a result, permeability.
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Javor, V. "On the Choice of the Lightning Channel Current Decay Constant in the Modified Transmission Line Model with Exponential Decay." Journal of Communications Software and Systems 5, no. 4 (December 20, 2009): 135. http://dx.doi.org/10.24138/jcomss.v5i4.199.
Повний текст джерелаАнотація:
For different values of the decay constant in the Modified Transmission Line Model with Exponential Decay (MTLE) and for dierent channel heights the results for lightningelectromagnetic field (LEMF) at dierent distances fromthe channel-base are presented in this paper, so as for the spatial and temporal current distribution along the channel. The decay constant influence on LEMF above perfectly conducting ground is analyzed using new lightning channel-base current function and MTLE as an engineering model for a lightning return stroke. The proper choice of this constant can be made based on experimental results but also on the analysis of its influence on electric and magnetic field values and their shape characteristics.
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Kopljar, Ivan, Alain J. Labro, Tessa de Block, Jon D. Rainier, Jan Tytgat, and Dirk J. Snyders. "The ladder-shaped polyether toxin gambierol anchors the gating machinery of Kv3.1 channels in the resting state." Journal of General Physiology 141, no. 3 (February 11, 2013): 359–69. http://dx.doi.org/10.1085/jgp.201210890.
Повний текст джерелаАнотація:
Voltage-gated potassium (Kv) and sodium (Nav) channels are key determinants of cellular excitability and serve as targets of neurotoxins. Most marine ciguatoxins potentiate Nav channels and cause ciguatera seafood poisoning. Several ciguatoxins have also been shown to affect Kv channels, and we showed previously that the ladder-shaped polyether toxin gambierol is a potent Kv channel inhibitor. Most likely, gambierol acts via a lipid-exposed binding site, located outside the K+ permeation pathway. However, the mechanism by which gambierol inhibits Kv channels remained unknown. Using gating and ionic current analysis to investigate how gambierol affected S6 gate opening and voltage-sensing domain (VSD) movements, we show that the resting (closed) channel conformation forms the high-affinity state for gambierol. The voltage dependence of activation was shifted by >120 mV in the depolarizing direction, precluding channel opening in the physiological voltage range. The (early) transitions between the resting and the open state were monitored with gating currents, and provided evidence that strong depolarizations allowed VSD movement up to the activated-not-open state. However, for transition to the fully open (ion-conducting) state, the toxin first needed to dissociate. These dissociation kinetics were markedly accelerated in the activated-not-open state, presumably because this state displayed a much lower affinity for gambierol. A tetrameric concatemer with only one high-affinity binding site still displayed high toxin sensitivity, suggesting that interaction with a single binding site prevented the concerted step required for channel opening. We propose a mechanism whereby gambierol anchors the channel’s gating machinery in the resting state, requiring more work from the VSD to open the channel. This mechanism is quite different from the action of classical gating modifier peptides (e.g., hanatoxin). Therefore, polyether toxins open new opportunities in structure–function relationship studies in Kv channels and in drug design to modulate channel function.
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Prod'hom, B., D. Pietrobon, and P. Hess. "Interactions of protons with single open L-type calcium channels. Location of protonation site and dependence of proton-induced current fluctuations on concentration and species of permeant ion." Journal of General Physiology 94, no. 1 (July 1, 1989): 23–42. http://dx.doi.org/10.1085/jgp.94.1.23.
Повний текст джерелаАнотація:
We further investigated the rapid fluctuations between two different conductance levels promoted by protons when monovalent ions carry current through single L-type Ca channels. We tested for voltage dependence of the proton-induced current fluctuations and for accessibility of the protonation site from both sides of the membrane patch. The results strongly suggest an extracellular location of the protonation site. We also studied the dependence of the kinetics of the fluctuations and of the two conductance levels on the concentration of permeant ion and on external ionic strength. We find that saturation curves of channel conductance vs. [K] are similar for the two conductance levels. This provides evidence that protonation does not appreciably change the surface potential near the entry of the permeation pathway. The proton-induced conduction change must therefore result from an indirect interaction between the protonation site and the ion-conducting pathway. Concentration of permeant ion and ionic strength also affect the kinetics of the current fluctuations, in a manner consistent with our previous hypothesis that channel occupancy destabilizes the low conductance channel conformation. We show that the absence of measurable fluctuations with Li and Ba as charge carriers can be explained by significantly higher affinities of these ions for permeation sites. Low concentrations of Li reduce the Na conductance and abbreviate the lifetimes of the low conductance level seen in the presence of Na. We use whole-cell recordings to extrapolate our findings to the physiological conditions of Ca channel permeation and conclude that in the presence of 1.8 mM Ca no proton-induced fluctuations occur between pH 7.5 and 6.5. Finally, we propose a possible physical interpretation of the formal model of the protonation cycle introduced in the companion paper.
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Beurg, Maryline, Wei Xiong, Bo Zhao, Ulrich Müller, and Robert Fettiplace. "Subunit determination of the conductance of hair-cell mechanotransducer channels." Proceedings of the National Academy of Sciences 112, no. 5 (December 30, 2014): 1589–94. http://dx.doi.org/10.1073/pnas.1420906112.
Повний текст джерелаАнотація:
Cochlear hair cells convert sound stimuli into electrical signals by gating of mechanically sensitive ion channels in their stereociliary (hair) bundle. The molecular identity of this ion channel is still unclear, but its properties are modulated by accessory proteins. Two such proteins are transmembrane channel-like protein isoform 1 (TMC1) and tetraspan membrane protein of hair cell stereocilia (TMHS, also known as lipoma HMGIC fusion partner-like 5, LHFPL5), both thought to be integral components of the mechanotransduction machinery. Here we show that, in mice harboring an Lhfpl5 null mutation, the unitary conductance of outer hair cell mechanotransducer (MT) channels was reduced relative to wild type, and the tonotopic gradient in conductance, where channels from the cochlear base are nearly twice as conducting as those at the apex, was almost absent. The macroscopic MT current in these mutants was attenuated and the tonotopic gradient in amplitude was also lost, although the current was not completely extinguished. The consequences of Lhfpl5 mutation mirror those due to Tmc1 mutation, suggesting a part of the MT-channel conferring a large and tonotopically variable conductance is similarly disrupted in the absence of Lhfpl5 or Tmc1. Immunolabelling demonstrated TMC1 throughout the stereociliary bundles in wild type but not in Lhfpl5 mutants, implying the channel effect of Lhfpl5 mutations stems from down-regulation of TMC1. Both LHFPL5 and TMC1 were shown to interact with protocadherin-15, a component of the tip link, which applies force to the MT channel. We propose that titration of the TMC1 content of the MT channel sets the gradient in unitary conductance along the cochlea.
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Tomić, Melanija, Marek Kucka, Karla Kretschmannova, Shuo Li, Maria Nesterova, Constantine A. Stratakis, and Stanko S. Stojilkovic. "Role of nonselective cation channels in spontaneous and protein kinase A-stimulated calcium signaling in pituitary cells." American Journal of Physiology-Endocrinology and Metabolism 301, no. 2 (August 2011): E370—E379. http://dx.doi.org/10.1152/ajpendo.00130.2011.
Повний текст джерелаАнотація:
Several receptors linked to the adenylyl cyclase signaling pathway stimulate electrical activity and calcium influx in endocrine pituitary cells, and a role for an unidentified sodium-conducting channel in this process has been proposed. Here we show that forskolin dose-dependently increases cAMP production and facilitates calcium influx in about 30% of rat and mouse pituitary cells at its maximal concentration. The stimulatory effect of forskolin on calcium influx was lost in cells with inhibited PKA (cAMP-dependent protein kinase) and in cells that were haploinsufficient for the main PKA regulatory subunit but was preserved in cells that were also haploinsufficient for the main PKA catalytic subunit. Spontaneous and forskolin-stimulated calcium influx was present in cells with inhibited voltage-gated sodium and hyperpolarization-activated cation channels but not in cells bathed in medium, in which sodium was replaced with organic cations. Consistent with the role of sodium-conducting nonselective cation channels in PKA-stimulated Ca2+ influx, cAMP induced a slowly developing current with a reversal potential of about 0 mV. Two TRP (transient receptor potential) channel blockers, SKF96365 and 2-APB, as well as flufenamic acid, an inhibitor of nonselective cation channels, also inhibited spontaneous and forskolin-stimulated electrical activity and calcium influx. Quantitative RT-PCR analysis indicated the expression of mRNA transcripts for TRPC1 >> TRPC6 > TRPC4 > TRPC5 > TRPC3 in rat pituitary cells. These experiments suggest that in pituitary cells constitutively active cation channels are stimulated further by PKA and contribute to calcium signaling indirectly by controlling the pacemaking depolarization in a sodium-dependent manner and directly by conducting calcium.
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Carmona, Emerson M., H. Peter Larsson, Alan Neely, Osvaldo Alvarez, Ramon Latorre, and Carlos Gonzalez. "Gating charge displacement in a monomeric voltage-gated proton (Hv1) channel." Proceedings of the National Academy of Sciences 115, no. 37 (August 20, 2018): 9240–45. http://dx.doi.org/10.1073/pnas.1809705115.
Повний текст джерелаАнотація:
The voltage-gated proton (Hv1) channel, a voltage sensor and a conductive pore contained in one structural module, plays important roles in many physiological processes. Voltage sensor movements can be directly detected by measuring gating currents, and a detailed characterization of Hv1 charge displacements during channel activation can help to understand the function of this channel. We succeeded in detecting gating currents in the monomeric form of the Ciona-Hv1 channel. To decrease proton currents and better separate gating currents from ion currents, we used the low-conducting Hv1 mutant N264R. Isolated ON-gating currents decayed at increasing rates with increasing membrane depolarization, and the amount of gating charges displaced saturates at high voltages. These are two hallmarks of currents arising from the movement of charged elements within the boundaries of the cell membrane. The kinetic analysis of gating currents revealed a complex time course of the ON-gating current characterized by two peaks and a marked Cole–Moore effect. Both features argue that the voltage sensor undergoes several voltage-dependent conformational changes during activation. However, most of the charge is displaced in a single central transition. Upon voltage sensor activation, the charge is trapped, and only a fast component that carries a small percentage of the total charge is observed in the OFF. We hypothesize that trapping is due to the presence of the arginine side chain in position 264, which acts as a blocking ion. We conclude that the movement of the voltage sensor must proceed through at least five states to account for our experimental data satisfactorily.
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Leal-Pinto, Edgar, Avelino Teixeira, Baohuong Tran, Basil Hanss, and Paul E. Klotman. "Presence of the nucleic acid channel in renal brush-border membranes: allosteric modulation by extracellular calcium." American Journal of Physiology-Renal Physiology 289, no. 1 (July 2005): F97—F106. http://dx.doi.org/10.1152/ajprenal.00196.2004.
Повний текст джерелаАнотація:
We have previously described a cell surface channel complex that is highly selective for nucleic acid ( 6 , 7 ). The channel complex was purified to homogeneity by solubilizing renal brush-border membranes (BBM) with CHAPS and separation by liquid chromatography. It was characterized by reconstitution in planar lipid bilayers. The channel consists of a pore-forming subunit that is blocked by heparan sulfate and a regulatory subunit that is blocked by l-malate ( 7 ). The current studies were performed to compare the characteristics of the nucleic acid-conducting channel in native BBM with the characteristics that have been determined for the complex reconstituted from purified proteins. BBM were purified by differential centrifugation and reconstituted in lipid bilayers. Current was not observed until oligodeoxynucleotide (ODN) was added. Conductance was 9.1 ± 0.9 pS; rectification and voltage dependence were not observed. Reversal potential ( Erev) shifted to +14 ± 0.1 mV by a 10-fold gradient for ODN but was not altered when gradients were created for any other ion. Open probability increased significantly with an increase in Ca2+ on the trans chamber of the bilayer apparatus. Changes in cis Ca2+ were without effect. Addition of l-malate to the cis chamber or heparan sulfate to the trans chamber significantly reduced the open probability of the channel. These data demonstrate that the nucleic acid channel in BBM is electrophysiologically and pharmacologically identical to that previously reported for purified protein and demonstrate that a nucleic acid-conducting channel is a component of renal BBM.
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Kerschbaum, Hubert H., and Michael D. Cahalan. "Monovalent Permeability, Rectification, and Ionic Block of Store-operated Calcium Channels in Jurkat T Lymphocytes." Journal of General Physiology 111, no. 4 (April 1, 1998): 521–37. http://dx.doi.org/10.1085/jgp.111.4.521.
Повний текст джерелаАнотація:
We used whole-cell recording to characterize ion permeation, rectification, and block of monovalent current through calcium release-activated calcium (CRAC) channels in Jurkat T lymphocytes. Under physiological conditions, CRAC channels exhibit a high degree of selectivity for Ca2+, but can be induced to carry a slowly declining Na+ current when external divalent ions are reduced to micromolar levels. Using a series of organic cations as probes of varying size, we measured reversal potentials and calculated permeability ratios relative to Na+, PX/PNa, in order to estimate the diameter of the conducting pore. Ammonium (NH4+) exhibited the highest relative permeability (PNH4/PNa = 1.37). The largest permeant ion, tetramethylammonium with a diameter of 0.55 nm, had PTMA/PNa of 0.09. N-methyl-d-glucamine (0.50 × 0.64 × 1.20 nm) was not measurably permeant. In addition to carrying monovalent current, NH4+ reduced the slow decline of monovalent current (“inactivation”) upon lowering [Ca2+]o. This kinetic effect of extracellular NH4+ can be accounted for by an increase in intracellular pH (pHi), since raising intracellular pH above 8 reduced the extent of inactivation. In addition, decreasing pHi reduced monovalent and divalent current amplitudes through CRAC channels with a pKa of 6.8. In several channel types, Mg2+ has been shown to produce rectification by a voltage-dependent block mechanism. Mg2+ removal from the pipette solution permitted large outward monovalent currents to flow through CRAC channels while also increasing the channel's relative Cs+ conductance and eliminating the inactivation of monovalent current. Boltzmann fits indicate that intracellular Mg2+ contributes to inward rectification by blocking in a voltage-dependent manner, with a zδ product of 1.88. Ca2+ block from the outside was also found to be voltage dependent with zδ of 1.62. These experiments indicate that the CRAC channel, like voltage-gated Ca2+ channels, achieves selectivity for Ca2+ by selective binding in a large pore with current–voltage characteristics shaped by internal Mg2+.
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Arreola, J., J. E. Melvin, and T. Begenisich. "Activation of calcium-dependent chloride channels in rat parotid acinar cells." Journal of General Physiology 108, no. 1 (July 1, 1996): 35–47. http://dx.doi.org/10.1085/jgp.108.1.35.
Повний текст джерелаАнотація:
The Ca2+ and voltage dependence of Ca(2+)-activated Cl- currents in rat parotid acinar cells was examined with the whole-cell patch clamp technique. Acinar cells were dialyzed with buffered free Ca2+ concentrations ([Ca2+]i) from < 1 nM to 5 microM. Increasing [Ca2+]i induced an increase in Cl- current at all membrane potentials. In cells dialyzed with [Ca2+]i > 25 nM, depolarizing test pulses activated a Cl- current that was composed of an instantaneous and a slow monoexponential component. The steady-state current-voltage relationship showed outward rectification at low [Ca2+]i but became more linear as the [Ca2+]i increased because of a shift in Cl- channel activation toward more negative voltages. The Ca2+ dependence of steady-state channel activation at various membrane voltages was fit by the Hill equation. The apparent Kd and Hill coefficient obtained from this analysis were both functions of membrane potential. The Kd decreased from 417 to 63 nM between -106 and +94 mV, whereas the Hill coefficient was always > 1 and increased to values as large as 2.5 at large positive potentials. We found that a relatively simple mechanistic model can account for the channel steady-state and kinetic behavior. In this model, channel activation involves two identical, independent, sequential Ca2+ binding steps before a final Ca(2+)-independent transition to the conducting conformation. Channel activation proceeds sequentially through three closed states before reaching the open state. The Ca2+ binding steps of this model have a voltage dependence similar to that of the Kd from the Hill analysis. The simplest interpretation of our findings is that these channels are directly activated by Ca2+ ions that bind to sites approximately 13% into the membrane electric field from the cytoplasmic surface.
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Javor, V., K. Lundengård, M. Rančić, and S. Silvestrov. "Application of Genetic Algorithm to Estimation of Function Parameters in Lightning Currents Approximations." International Journal of Antennas and Propagation 2017 (2017): 1–11. http://dx.doi.org/10.1155/2017/4937943.
Повний текст джерелаАнотація:
Genetic algorithm (GA) is applied for the estimation of two-peaked analytically extended function (2P-AEF) parameters in this paper. 2P-AEF is used for approximation of measured and typical lightning discharge currents. Lightning discharge channel is often modeled as thin-wire vertical antenna at perfectly conducting ground. Engineering lightning stroke models assume that the current along that channel is related to the channel-base current which may be measured at the instrumented tall towers and in triggered lightning experiments. Mathematical modeling of lightning currents is important in verification of lightning strokes models based on simultaneously measured electromagnetic fields at various distances, so as in lightning protection studies, computation of lightning induced effects and simulation of overvoltages in power systems. Typical lightning discharge currents of the first positive, first negative, and subsequent negative strokes are defined by IEC 62305 Standard based on comprehensive measurements. Parameters of 2P-AEF’s approximation of the typical negative first stroke current are determined by GA and compared to approximations obtained by other functions. Measured currents at Monte San Salvatore in Switzerland, at Morro de Cachimbo Station in Brazil, and in rocket-triggered lightning experiments at Camp Blanding in Florida are approximated by 2P-AEFs, and good agreement with experimentally measured waveshapes is obtained.
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UHM, HAN S., E. H. CHOI, J. J. KO, H. M. SHIN, and G. S. CHO. "Influence of ion density on electron-beam propagation from a gas-filled diode." Journal of Plasma Physics 61, no. 1 (January 1999): 31–41. http://dx.doi.org/10.1017/s0022377898007259.
Повний текст джерелаАнотація:
Electron-beam propagation from a gas-filled diode is investigated. The beginning portion of the electron beam pulse creates an ion channel not only inside the diode but also in the region beyond the anode. A theoretical model is developed for the space-charge-limited current of a relativistic electron beam propagating through an ion channel. A simple analytical expression for the space-charge-limited current is obtained within the context of a thin-beam approximation, where the conducting-tube radius is much larger than the beam radius. The beam current propagating through an ion channel is measured experimentally for a mildly relativistic electron beam. Whenever the ion density inside the diode is the same as the beam electron density, the diode is short-circuited. The ion-channel density at the short-circuiting time is calculated numerically and is used to estimate the space-charge-limited current. It is shown that the experimental data agree well with the analytical results predicted by the theoretical model.
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Chepilko, S., H. Zhou, H. Sackin, and L. G. Palmer. "Permeation and gating properties of a cloned renal K+ channel." American Journal of Physiology-Cell Physiology 268, no. 2 (February 1, 1995): C389—C401. http://dx.doi.org/10.1152/ajpcell.1995.268.2.c389.
Повний текст джерелаАнотація:
The renal K+ channel (ROMK2) was expressed in Xenopus oocytes, and the patch-clamp technique was used to assess its conducting and gating properties. In cell-attached patches with 110 mM K+ in the bath and pipette, the reversal potential was near zero and the inward conductance (36 pS) was larger than the outward conductance (17 pS). In excised inside-out patches the channels showed rectification in the presence of 5 mM Mg2+ on the cytoplasmic side but not in Mg(2+)-free solution. Inward currents were also observed when K+ was replaced in the pipette by Rb+, NH4+, or thallium (Tl+). The reversal potentials under these conditions yielded a selectivity sequence of Tl+ > K+ > Rb+ > NH4+. On the other hand, the slope conductances for inward current gave a selectivity sequence of K+ = NH4+ > Tl+ > Rb+. The differences in the two sequences can be explained by the presence of cation binding sites within the channel, which interact with Rb+ and Tl+ more strongly and with NH4+ less strongly than with K+. Two other ions, Ba2+ and Cs+, blocked the channel from the outside. The effect of Ba2+ (1 mM) was to reduce the open probability of the channels, whereas Cs+ (10 mM) reduced the apparent single-channel current. The effects of both blockers are enhanced by membrane hyperpolarization. The kinetics of the channel were also studied in cell-attached patches. With K+ in the pipette the distribution of open times could be described by a single exponential (tau 0 = 25 ms), whereas two exponentials (tau 1 = 1 ms, tau 2 = 30 ms) were required to describe the closed-time distribution. Hyperpolarization of the oocyte membrane decreased the open probability and tau 0, and increased tau 1, tau 2, and the number of long closures. The presence of Tl+ in the pipette significantly altered the kinetics, reducing tau 0 and eliminating the long-lived closures. These results suggest that the gating of the channel may depend on the nature of the ion in the pore.
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Amcheslavsky, Anna, Olga Safrina, and Michael D. Cahalan. "State-dependent block of Orai3 TM1 and TM3 cysteine mutants: Insights into 2-APB activation." Journal of General Physiology 143, no. 5 (April 14, 2014): 621–31. http://dx.doi.org/10.1085/jgp.201411171.
Повний текст джерелаАнотація:
After endoplasmic reticulum (ER) Ca2+ store depletion, Orai channels in the plasma membrane (PM) are activated directly by ER-resident stromal interacting molecule (STIM) proteins to form the Ca2+-selective Ca2+ release-activated Ca2+ (CRAC) channel. Of the three human Orai channel homologues, only Orai3 can be activated by high concentrations (>50 µM) of 2-aminoethyl diphenylborinate (2-APB). 2-APB activation of Orai3 occurs without STIM1–Orai3 interaction or store depletion, and results in a cationic, nonselective current characterized by biphasic inward and outward rectification. Here we use cysteine scanning mutagenesis, thiol-reactive reagents, and patch-clamp analysis to define the residues that assist in formation of the 2-APB–activated Orai3 pore. Mutating transmembrane (TM) 1 residues Q83, V77, and L70 to cysteine results in potentiated block by cadmium ions (Cd2+). TM1 mutants E81C, G73A, G73C, and R66C form channels that are not sensitive to 2-APB activation. We also find that Orai3 mutant V77C is sensitive to block by 2-aminoethyl methanethiosulfonate (MTSEA), but not 2-(trimethylammonium)ethyl methanethiosulfonate (MTSET). Block induced by reaction with MTSEA is state dependent, as it occurs only when Orai3-V77C channels are opened by either 2-APB or by cotransfection with STIM1 and concurrent passive store depletion. We also analyzed TM3 residue E165. Mutation E165A in Orai3 results in diminished 2-APB–activated currents. However, it has little effect on store-operated current density. Furthermore, mutation E165C results in Cd2+-induced block that is state dependent: Cd2+ only blocks 2-APB–activated, not store-operated, mutant channels. Our data suggest that the dilated pore of 2-APB–activated Orai3 is lined by TM1 residues, but also allows for TM3 E165 to approach the central axis of the channel that forms the conducting pathway, or pore.
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Lyashchenko, Alex K., and Gareth R. Tibbs. "Ion binding in the Open HCN Pacemaker Channel Pore: Fast Mechanisms to Shape “Slow” Channels." Journal of General Physiology 131, no. 3 (February 11, 2008): 227–43. http://dx.doi.org/10.1085/jgp.200709868.
Повний текст джерелаАнотація:
IH pacemaker channels carry a mixed monovalent cation current that, under physiological ion gradients, reverses at ∼−34 mV, reflecting a 4:1 selectivity for K over Na. However, IH channels display anomalous behavior with respect to permeant ions such that (a) open channels do not exhibit the outward rectification anticipated assuming independence; (b) gating and selectivity are sensitive to the identity and concentrations of externally presented permeant ions; (c) the channels' ability to carry an inward Na current requires the presence of external K even though K is a minor charge carrier at negative voltages. Here we show that open HCN channels (the hyperpolarization-activated, cyclic nucleotide sensitive pore forming subunits of IH) undergo a fast, voltage-dependent block by intracellular Mg in a manner that suggests the ion binds close to, or within, the selectivity filter. Eliminating internal divalent ion block reveals that (a) the K dependence of conduction is mediated via K occupancy of site(s) within the pore and that asymmetrical occupancy and/or coupling of these sites to flux further shapes ion flow, and (b) the kinetics of equilibration between K-vacant and K-occupied states of the pore (10–20 μs or faster) is close to the ion transit time when the pore is occupied by K alone (∼0.5–3 μs), a finding that indicates that either ion:ion repulsion involving Na is adequate to support flux (albeit at a rate below our detection threshold) and/or the pore undergoes rapid, permeant ion-sensitive equilibration between nonconducting and conducting configurations. Biophysically, further exploration of the Mg site and of interactions of Na and K within the pore will tell us much about the architecture and operation of this unusual pore. Physiologically, these results suggest ways in which “slow” pacemaker channels may contribute dynamically to the shaping of fast processes such as Na-K or Ca action potentials.