Voltage-sensing domains: structural and functional diversity

Voltage-sensing domains (VSDs) are structural modules of voltage-gated ion channels, which sense changes in the membrane potential and, in response, open and close the channel's ion conduction pore. VSDs comprise a bundle of four antiparallel transmembrane helices (S1-S4). Their basic function is well described by the sliding helix model. Upon membrane depolarization, the positively charged S4 helix slides upward and several of its positive gating charges cross the focused membrane electric field. This state transition is conformationally coupled to the opening of the channel gate. While this essential mechanism is common to all VSDs, different VSDs display a considerable structural and functional diversity, including the number of the gating charges, the nature of their countercharges, and the range, speed, and voltage dependence of the S4 movement upon activation. Here, we review these differences and discuss how they might function to determine the distinct gating properties of voltage-gated ion channels.