Molecular regulation of voltage-gated Ca2+ channels

Voltage-gated Ca2+ (Ca-V) channels are found in all excitable cells and many nonexcitable cells, in which they govern Ca2+ influx, thereby contributing to determine a host of important physiological processes including gene transcription, muscle contraction, hormone secretion, and neurotransmitter release. The past years have seen some significant advances in our understanding of the functional, pharmacological, and molecular properties of Ca-V channels. Molecular studies have revealed that several of these channels are oligomeric complexes consisting of an ion-conducting alpha(1) subunit and auxiliary alpha(2)delta, beta, and gamma subunits. In addition, cloning of multiple Ca-V channel alpha(1) subunits has offered the opportunity to investigate the regulation of these proteins at the molecular level. The regulation of Ca-V channels by intracellular second messengers constitutes a key mechanism for controlling Ca2+ influx. This review summarizes recent advances that have provided important clues to the underlying molecular mechanisms involved in the regulation of Ca-V channels by protein phosphorylation, G-protein activation, and interactions with Ca2+-binding and SNARE proteins.