Abstract
Voltage-gated calcium channels are multi-pass transmembrane proteins that have key features that are essential for their correct function. For example, the concerted movement of the voltage sensor domains in response to depolarization is required to ensure the channels open over a particular range of voltages, essential for the physiological function of each of the 10 different mammalian calcium channels. Furthermore, their selectivity filter is required to maintain the Ca(2+) selectivity of these channels. The auxiliary subunits, α(2)δ and β, play important roles in aiding the channels to fold, traffic and function correctly. Of therapeutic importance, the α(2)δ subunits are a drug target of the gabapentinoid α(2)δ ligands, whose mechanism of action is now better understood. However, much is still unknown about how these calcium channels reach and are retained in specific locations, and how these processes are modified by various forms of modulation and synaptic plasticity.