Voltage sensors of a Na+ channel dissociate from the pore domain and form inter-channel dimers in the resting state

Ayumi Sumino (), Takashi Sumikama (), Mikihiro Shibata and Katsumasa Irie ()
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Ayumi Sumino: Kanazawa University
Takashi Sumikama: Kanazawa University
Mikihiro Shibata: Kanazawa University
Katsumasa Irie: Wakayama Medical University

Nature Communications, 2023, vol. 14, issue 1, 1-11

Abstract: Abstract Understanding voltage-gated sodium (Nav) channels is significant since they generate action potential. Nav channels consist of a pore domain (PD) and a voltage sensor domain (VSD). All resolved Nav structures in different gating states have VSDs that tightly interact with PDs; however, it is unclear whether VSDs attach to PDs during gating under physiological conditions. Here, we reconstituted three different voltage-dependent NavAb, which is cloned from Arcobacter butzleri, into a lipid membrane and observed their structural dynamics by high-speed atomic force microscopy on a sub-second timescale in the steady state. Surprisingly, VSDs dissociated from PDs in the mutant in the resting state and further dimerized to form cross-links between channels. This dimerization would occur at a realistic channel density, offering a potential explanation for the facilitation of positive cooperativity of channel activity in the rising phase of the action potential.

Date: 2023
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DOI: 10.1038/s41467-023-43347-3

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