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, Katsumasa Irie
Abstract
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 v Ab, 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.