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September 22, 2008Proceedings of the National Academy of SciencesOpen Access

Disulfide locking a sodium channel voltage sensor reveals ion pair formation during activation

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Population

Bacterial sodium channel NaChBac

Comparison

Paired cysteine substitutions for the third… vs Single cysteine mutants

Design

Preclinical

Key result

Paired cysteine substitutions (D60C:R3C) in the bacterial sodium channel NaChBac form a disulfide bond during activation, revealing voltage-dependent formation of an ion pair in real time.

Authors

PDPaul G. DeCaenVYVladimir Yarov‐YarovoyYZYong Zhao

Discussion

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Overview

Supports bacterial NaV gating model; leaves open relevance to human cardiac channelopathies.

Structured PICO

P
Population
Bacterial sodium channel NaChBac
I
Intervention
Paired cysteine substitutions for the third gating charge (R3) in S4 and D60 in S2 (D60C:R3C)
C
Comparator
Single cysteine mutants
O
Outcome
Disulfide bond formation and channel activation kineticssurrogate

Demonstrates real-time voltage-dependent formation of an ion pair during activation of the voltage sensor, suggesting this interaction catalyzes S4 movement.

Cite This Study

DeCaen et al. (2008) studied this question. Paired cysteine substitutions (D60C:R3C) in NaChBac vs. Single cysteine mutants was evaluated on Disulfide bond formation and channel activation kinetics. Paired cysteine substitutions (D60C:R3C) in the bacterial sodium channel NaChBac form a disulfide bond during activation, revealing voltage-dependent formation of an ion pair in real time.

synapsesocial.com/papers/6a6305bbf2b26b064709504ahttps://doi.org/10.1073/pnas.0806486105
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