Molecular movements underlying voltage-dependent regulation of the CaV2.1 channel

Abstract

P/Q-type, voltage-gated Ca2+ channels (CaV2.1) are the dominant CaV isoform in the brain and mediate excitation-evoked neurotransmitter release. They are also thought to contribute to plasticity (short-term presynaptic depression) via their process of voltage-dependent inactivation (VDI). Recent atomistic CaV structures revealed the high structural complexity of these molecular machines, yet the sources of voltage dependence of channel opening and VDI remain unclear. We hypothesize that they arise from the movements of the four homologous, but non-identical voltage-sensing domains (VSDs).