A Rich Conformational Palette Underlies Human Ca_V2.1-Channel Availability.

ABSTRACT: Depolarization-evoked opening of Ca_V2.1 (P/Q-type) Ca²⁺-channels triggers neurotransmitter release, while voltage-dependent inactivation (VDI) limits channel availability to open, contributing to synaptic plasticity. The mechanism of Ca_V2.1 response to voltage is unclear. Using voltage-clamp fluorometry and kinetic modeling, we optically tracked and physically characterized the structural dynamics of the four Ca_V2.1 voltage-sensor domains (VSDs). VSD-I seems to directly drive opening and convert between two modes of function, associated with VDI. VSD-II is apparently voltage-insensitive. VSD-III and VSD-IV sense more negative voltages and undergo voltage-dependent conversion uncorrelated with VDI. Auxiliary β -subunits regulate VSD-I-to-pore coup

SUBMITTER: Wang K 

PROVIDER: S-EPMC11507735 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature