Structure-function relationship of the voltage-gated calcium channel Ca_v1.1 complex

Voltage-gated calcium (Ca_v) channels are miniature membrane transistors that convert membrane electrical signals to intracellular Ca²⁺ transients that trigger many physiological events. In mammals, there are ten subtypes of Ca_v channel, among which Ca_v1.1 is the first Ca_vα1 to be cloned. Ca_v1.1 is specified for the excitation–contraction coupling of skeletal muscles, and has been a prototype in the structural investigations of Ca_v channels. This article summarized the recent advances in the structural elucidation of Ca_v1.1 and the mechanistic insights derived from the 3.6 Å structure obtained using single-particle, electron cryomicroscopy. The structure of the Ca_v1.1 complex established the framework for mechanistic understanding of excitation–contraction coupling and provides the template for molecular interpretations of the functions and disease mechanisms of Ca_v and Na_v channels.