Activation and closed-state inactivation mechanisms of the human voltage-gated K_V4 channel complexes.

ABSTRACT: The voltage-gated ion channel activity depends on both activation (transition from the resting state to the open state) and inactivation. Inactivation is a self-restraint mechanism to limit ion conduction and is as crucial to membrane excitability as activation. Inactivation can occur when the channel is open or closed. Although open-state inactivation is well understood, the molecular basis of closed-state inactivation has remained elusive. We report cryo-EM structures of human K_V4.2 channel complexes in inactivated, open, and closed states. Closed-state inactivation of K_V4 involves an unprecedented symmetry breakdown for pore closure by only two of the four S4-S5 linkers, distinct from known mechanisms of open-state inactivation. We further capture K_V4 in

SUBMITTER: Ye W 

PROVIDER: S-EPMC9271590 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature