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

ABSTRACT: Understanding voltage-gated sodium (Na_v) channels is significant since they generate action potential. Na_v channels consist of a pore domain (PD) and a voltage sensor domain (VSD). All resolved Na_v 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 Na_vAb, 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.

SUBMITTER: Sumino A 

PROVIDER: S-EPMC10730821 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature