Molecular Mechanism of Cooperative Opening of Voltage-gated Sodium Channels

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 show VSDs that tightly interact with PDs; however, it is unclear whether VSDs attach to PDs during gating under physiological conditions. Recently, we observed structural dynamics of three different voltage-dependent NavAb by high-speed atomic force microscopy. Surprisingly, VSDs dissociated from PDs in the resting state and dimerized between channels. This dimerization would be a potential explanation for the facilitation of cooperative activation in the rising phase of the action potential.