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December 1, 1996The Journal of General PhysiologyOpen Access

A unique role for the S4 segment of domain 4 in the inactivation of sodium channels.

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Population

Human heart Na+ channel model

Design

Preclinical

Authors

LCL Q ChenUniversity of PennsylvaniaVSVincent P. SantarelliMerck & Co., Inc., Rahway, NJ, USA (United States)RHR HornZoological Society of San Diego

Discussion

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Implication

S4D4 may represent a selective target in NaV1.5-related arrhythmias; leaves open whether findings translate beyond animal models.

Structured PICO

P
Population
Human heart Na+ channel model
I
Intervention
15 charge-neutralizing or -reversing substitutions in the first or third basic residues (arginine or lysine) by replacement with histidine, glutamine, or glutamate in S4 segments of each domain
O
Outcome
Voltage dependence of peak Na+ current, steady-state inactivation, and inactivation time constantssurrogate

Mutations in the S4 segment of domain 4 of the human heart sodium channel demonstrate its unique role in activation-inactivation coupling.

Cite This Study

Chen et al. (1996) studied this question.

synapsesocial.com/papers/6a709cc7c2d7c3090826f086https://doi.org/10.1085/jgp.108.6.549
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Also Consider

Synapse has enriched 3 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Inactivation viewed through single sodium channels.1984 · 163 citations
  2. 2Voltage gating of ion channels1994 · 415 citations
  3. 3Direct Physical Measure of Conformational Rearrangement Underlying Potassium Channel Gating1996 · 617 citations