Abstract
Voltage-gated Ca(2+) (Ca(V)) channels mediate Ca(2+) ions influx into cells in response to depolarization of the plasma membrane. They are responsible for initiation of excitation-contraction and excitation-secretion coupling, and the Ca(2+) that enters cells through this pathway is also important in the regulation of protein phosphorylation, gene transcription, and many other intracellular events. Initial electrophysiological studies divided Ca(V) channels into low-voltage-activated (LVA) and high-voltage-activated (HVA) channels. The HVA Ca(V) channels were further subdivided into L, N, P/Q, and R-types which are oligomeric protein complexes composed of an ion-conducting Ca(V)α(1) subunit and auxiliary Ca(V)α(2)δ, Ca(V)β, and Ca(V)γ subunits. The functional consequences of the auxiliary subunits include altered functional and pharmacological properties of the channels as well as increased current densities. The latter observation suggests an important role of the auxiliary subunits in membrane trafficking of the Ca(V)α(1) subunit. This includes the mechanisms by which Ca(V) channels are targeted to the plasma membrane and to appropriate regions within a given cell. Likewise, the auxiliary subunits seem to participate in the mechanisms that remove Ca(V) channels from the plasma membrane for recycling and/or degradation. Diverse studies have provided important clues to the molecular mechanisms involved in the regulation of Ca(V) channels by the auxiliary subunits, and the roles that these proteins could possibly play in channel targeting and membrane Stabilization.