Ca_V1.1 voltage-sensing domain III exclusively controls skeletal muscle excitation-contraction coupling.

ABSTRACT: Skeletal muscle contractions are initiated by action potentials, which are sensed by the voltage-gated calcium channel (Ca_V1.1) and are conformationally coupled to calcium release from intracellular stores. Notably, Ca_V1.1 contains four separate voltage-sensing domains (VSDs), which activate channel gating and excitation-contraction (EC-) coupling at different voltages and with distinct kinetics. Here we show that a single VSD of Ca_V1.1 controls skeletal muscle EC-coupling. Whereas mutations in VSDs I, II and IV affect the current properties but not EC-coupling, only mutations in VSD III alter the voltage-dependence of depolarization-induced calcium release. Molecular dynamics simulations reveal comprehensive, non-canonical state transitions of VSD III in r

SUBMITTER: Pelizzari S 

PROVIDER: S-EPMC11358481 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature