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August 1, 1999The Journal of General PhysiologyOpen Access

Movement of Voltage Sensor S4 in Domain 4 Is Tightly Coupled to Sodium Channel Fast Inactivation and Gating Charge Immobilization

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Population

Xenopus oocytes expressing rat brain IIA sodium channels

Comparison

Site-directed mutagenesis of the central… vs Wild-type rat brain IIA sodium channels

Design

Preclinical

Authors

FKFrank KühnTU Dortmund UniversityNGNikolaus G. GreeffUniversity of Vermont

Discussion

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Overview

Extends basic understanding of NaV channel gating in animal models; leaves open translation to human channelopathies or therapies.

Structured PICO

P
Population
Xenopus oocytes expressing rat brain IIA sodium channels
I
Intervention
Site-directed mutagenesis of the central arginine residues to histidine in the S4D4 voltage sensor (R1635H, R1638H, R1635/1638H)
C
Comparator
Wild-type rat brain IIA sodium channels
O
Outcome
Correlation of fast inactivation and the movement of the S4D4 voltage sensor measured by ionic and gating currentssurrogate

The S4D4 voltage sensor in sodium channels is tightly coupled to fast inactivation and gating charge immobilization.

Cite This Study

Kühn et al. (1999) studied this question.

synapsesocial.com/papers/6a71a0c7439bab0cabc3a23dhttps://doi.org/10.1085/jgp.114.2.167
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1A unique role for the S4 segment of domain 4 in the inactivation of sodium channels.1996 · 202 citations
  2. 2Sodium channel mutations in paramyotonia congenita uncouple inactivation from activation1994 · 344 citations
  3. 3Histidine residues at the N- and C-termini of .alpha.-helixes: perturbed pKas and protein stability1992 · 123 citations
  4. 4A quantitative description of membrane current and its application to conduction and excitation in nerve1952 · 23,527 citations
  5. 5Slow Inactivation Does Not Affect Movement of the Fast Inactivation Gate in Voltage-gated Na+ Channels1998 · 73 citations