Abstract
Ion channels are essential for cellular signaling. Voltage-gated ion channels (VGICs) are the largest and most extensively studied superfamily of ion channels. They possess modular structural features such as voltage-sensing domains that encircle and form mechanical connections with the pore-forming domains. Such features are intimately related to their function in sensing and responding to changes in the membrane potential. In the present work, we discuss the thermodynamic mechanisms of the VGIC superfamily, including the two-state gating mechanism, sliding-rocking mechanism of the voltage sensor, subunit cooperation, lipid-infiltration mechanism of inactivation, and the relationship with their structural features.