scholarly journals Metal Bridge in S4 Segment Supports Helix Transition in Shaker Channel

2020 ◽  
Vol 118 (4) ◽  
pp. 922-933 ◽  
Author(s):  
Carlos A.Z. Bassetto ◽  
João Luis Carvalho-de-Souza ◽  
Francisco Bezanilla
Keyword(s):  
S4 Segment

scholarly journals Role of the S4 Segment in a Voltage-dependent Calcium-sensitive Potassium (hSlo) Channel

1998 ◽  
Vol 273 (49) ◽  
pp. 32430-32436 ◽  
Author(s):  
Laı́n Dı́az ◽  
Pratap Meera ◽  
Julio Amigo ◽  
Enrico Stefani ◽  
Osvaldo Alvarez ◽  
...  
Keyword(s):  
Voltage Dependent ◽  
S4 Segment

scholarly journals Gating Pore Currents in DIIS4 Mutations of NaV1.4 Associated with Periodic Paralysis: Saturation of Ion Flux and Implications for Disease Pathogenesis

2008 ◽  
Vol 132 (4) ◽  
pp. 447-464 ◽  
Author(s):  
Arie F. Struyk ◽  
Vladislav S. Markin ◽  
David Francis ◽  
Stephen C. Cannon
Keyword(s):  
Periodic Paralysis ◽  
Cation Binding ◽  
Resting Potential ◽  
Inward Rectification ◽  
Missense Mutations ◽  
Ionic Selectivity ◽  
Cation Selectivity ◽  
Cation Binding Site ◽  
Biophysical Profile ◽  
S4 Segment

S4 voltage–sensor mutations in CaV1.1 and NaV1.4 channels cause the human muscle disorder hypokalemic periodic paralysis (HypoPP). The mechanism whereby these mutations predispose affected sarcolemma to attacks of sustained depolarization and loss of excitability is poorly understood. Recently, three HypoPP mutations in the domain II S4 segment of NaV1.4 were shown to create accessory ionic permeation pathways, presumably extending through the aqueous gating pore in which the S4 segment resides. However, there are several disparities between reported gating pore currents from different investigators, including differences in ionic selectivity and estimates of current amplitude, which in turn have important implications for the pathological relevance of these aberrant currents. To clarify the features of gating pore currents arising from different DIIS4 mutants, we recorded gating pore currents created by HypoPP missense mutations at position R666 in the rat isoform of Nav1.4 (the second arginine from the outside, at R672 in human NaV1.4). Extensive measurements were made for the index mutation, R666G, which created a gating pore that was permeable to K+ and Na+. This current had a markedly shallow slope conductance at hyperpolarized voltages and robust inward rectification, even when the ionic gradient strongly favored outward ionic flow. These characteristics were accounted for by a barrier model incorporating a voltage-gated permeation pathway with a single cation binding site oriented near the external surface of the electrical field. The amplitude of the R666G gating pore current was similar to the amplitude of a previously described proton-selective current flowing through the gating pore in rNaV1.4-R663H mutant channels. Currents with similar amplitude and cation selectivity were also observed in R666S and R666C mutant channels, while a proton-selective current was observed in R666H mutant channels. These results add support to the notion that HypoPP mutations share a common biophysical profile comprised of a low-amplitude inward current at the resting potential that may contribute to the pathological depolarization during attacks of weakness.

scholarly journals Dynamics of Pore Domain Affected by Single Mutations in S4 Segment of Shaker Potassium Channel

2019 ◽  
Vol 116 (3) ◽  
pp. 101a
Author(s):  
Carlos Alberto ◽  
Z. Bassetto Jr ◽  
Joao Luis Carvalho-de-Souza ◽  
Francisco Bezanilla
Keyword(s):  
Potassium Channel ◽  
Shaker Potassium Channel ◽  
Pore Domain ◽  
S4 Segment

scholarly journals Gating Consequences of Charge Neutralization of Arginine Residues in the S4 Segment of Kv7.2, an Epilepsy-Linked K+ Channel Subunit

2008 ◽  
Vol 95 (5) ◽  
pp. 2254-2264 ◽  
Author(s):  
Francesco Miceli ◽  
Maria Virginia Soldovieri ◽  
Ciria C. Hernandez ◽  
Mark S. Shapiro ◽  
Lucio Annunziato ◽  
...  
Keyword(s):  
K Channel ◽  
Charge Neutralization ◽  
Arginine Residues ◽  
S4 Segment

scholarly journals Gating Currents from Neuronal KV7 Channels Carrying BFNS-Causing Mutations in the S4 Segment of the Voltage Sensing Domain

2011 ◽  
Vol 100 (3) ◽  
pp. 426a
Author(s):  
Francesco Miceli ◽  
Ernesto Vargas ◽  
Maria Roberta Cilio ◽  
Francisco Bezanilla ◽  
Maurizio Taglialatela
Keyword(s):  
Gating Currents ◽  
Voltage Sensing ◽  
Kv7 Channels ◽  
Voltage Sensing Domain ◽  
S4 Segment

scholarly journals Voltage-insensitive Gating after Charge-neutralizing Mutations in the S4 Segment of Shaker Channels

1999 ◽  
Vol 113 (1) ◽  
pp. 139-151 ◽  
Author(s):  
Hongxia Bao ◽  
Atiya Hakeem ◽  
Mark Henteleff ◽  
John G. Starkus ◽  
Martin D. Rayner
Keyword(s):  
Single Channel ◽  
Voltage Sensor ◽  
Control Voltage ◽  
Shaker Channels ◽  
Open Time ◽  
Channel Opening ◽  
Electrostatic Coupling ◽  
And Control ◽  
Pore Domain ◽  
S4 Segment

Shaker channel mutants, in which the first (R362), second (R365), and fourth (R371) basic residues in the S4 segment have been neutralized, are found to pass potassium currents with voltage-insensitive kinetics when expressed in Xenopus oocytes. Single channel recordings clarify that these channels continue to open and close from −160 to +80 mV with a constant opening probability (Po). Although Po is low (∼0.15) in these mutants, mean open time is voltage independent and similar to that of control Shaker channels. Additionally, these mutant channels retain characteristic Shaker channel selectivity, sensitivity to block by 4-aminopyridine, and are partially blocked by external Ca2+ ions at very negative potentials. Furthermore, mean open time is approximately doubled, in both mutant channels and control Shaker channels, when Rb+ is substituted for K+ as the permeant ion species. Such strong similarities between mutant channels and control Shaker channels suggests that the pore region has not been substantially altered by the S4 charge neutralizations. We conclude that single channel kinetics in these mutants may indicate how Shaker channels would behave in the absence of voltage sensor input. Thus, mean open times appear primarily determined by voltage-insensitive transitions close to the open state rather than by voltage sensor movement, even in control, voltage-sensitive Shaker channels. By contrast, the low and voltage-insensitive Po seen in these mutant channels suggests that important determinants of normal channel opening derive from electrostatic coupling between S4 charges and the pore domain.

scholarly journals Structural dynamics determine voltage and pH gating in human voltage-gated proton channel

2021 ◽  
Author(s):  
Shuo Han ◽  
Sophia Peng ◽  
Joshua Vance ◽  
Kimberly Tran ◽  
Nhu Do ◽  
...  
Keyword(s):  
Ion Channels ◽  
Real Time ◽  
Conformational Dynamics ◽  
Conformational Transitions ◽  
Extracellular Ph ◽  
Voltage Sensors ◽  
Voltage Gated ◽  
Voltage Gated Ion Channels ◽  
S4 Segment ◽  
Gated Ion Channels

AbstractVoltage-gated ion channels are key players of electrical signaling in cells. As a unique subfamily, voltage-gated proton (Hv) channels are standalone voltage sensors without separate ion conductive pores. They are gated by both voltage and transmembrane proton gradient (i.e ΔpH), serving as acid extruders in most cells. Amongst their many functions, Hv channels are known to regulate the intracellular pH of human spermatozoa and compensate for the charge and pH imbalances caused by NADPH oxidases in phagocytes. Like the canonical voltage sensors, the Hv channel is a bundle of 4 helices (named S1 through S4), with the S4 segment carrying 3 positively charged Arg residues. Extensive structural and electrophysiological studies on voltage-gated ion channels generally agree on an outwards movement of the S4 segment upon activating voltage, but the real time conformational transitions are still unattainable. With purified human voltage-gated proton (hHv1) channel reconstituted in liposomes, we have examined its conformational dynamics at different voltage and pHs using the single molecule fluorescence resonance energy transfer (smFRET). Here we provided the first glimpse of real time conformational trajectories of the hHv1 voltage sensor and showed that both voltage and pH gradient shift the conformational dynamics of the S4 segment to control channel gating. Our results suggested the biological gating is determined by the conformational distributions of the hHv1 voltage sensor, rather than the conformational transitions between the presumptive ‘resting’ and ‘activated’ conformations. We further identified H140 as the key residue sensing extracellular pH and showed that both the intracellular and extracellular pH sensors act on the voltage sensing S4 segment to enrich the resting conformations. Taken together, we proposed a model that explains the mechanisms underlying voltage and pH gating in Hv channels, which may also serve as a general framework to understand the voltage sensing and gating in other voltage-gated ion channels.

Voltage sensing in jellyfish Shaker K+ channels.

1997 ◽  
Vol 200 (22) ◽  
pp. 2919-2926 ◽  
Author(s):  
N G Grigoriev ◽  
J D Spafford ◽  
W J Gallin ◽  
A N Spencer
Keyword(s):  
Segment Length ◽  
Total Charge ◽  
Fast Inactivation ◽  
Activation Curve ◽  
Channel Activation ◽  
Polyorchis Penicillatus ◽  
Shaker Channels ◽  
Critical Residue ◽  
S4 Segment ◽  
Positively Charged

The S4 segment of the jellyfish (Polyorchis penicillatus) Shaker channel jShak1 contains only six positively charged motifs. All other Shaker channels, including the jellyfish Shaker channel jShak2, have seven charges in this segment. Despite their charge differences, both these jellyfish channels produce currents with activation and inactivation curves shifted by approximately +40 mV relative to other Shaker currents. Adding charge without changing segment length by mutating the N-terminal side of jShak1 S4 does not have a pronounced effect on channel activation properties. Adding the positively charged motif RIF on the N-terminal side of K294 (the homologue of K374 in Drosophila Shaker, which is a structurally critical residue) produced a large positive shift in both activation and inactivation without altering the slope of the activation curve of the channel. When IFR was added to the other side of K294, there was a small negative shift in activation and fast inactivation of the channel was prevented. Our results demonstrate that K294 divides the S4 segment into functionally different regions and that the voltage threshold for activation and inactivation of the channel is not determined by the total charge on S4.

scholarly journals 310-Helix Conformation Facilitates the Transition of a Voltage Sensor S4 Segment toward the Down State

2011 ◽  
Vol 100 (6) ◽  
pp. 1446-1454 ◽  
Author(s):  
Christine S. Schwaiger ◽  
Pär Bjelkmar ◽  
Berk Hess ◽  
Erik Lindahl
Keyword(s):  
Voltage Sensor ◽  
Helix Conformation ◽  
S4 Segment ◽  
310 Helix
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