Voltage-gated Calcium Channels (Ca_V)

Voltage-gated calcium channels (Ca_V) are present in the membrane of most excitable cells and mediate calcium influx in response to depolarization. They regulate processes such as muscle contraction, secretion, neurotransmission and gene expression.

Ca_V channels are formed from four or five distinct subunits: α₁, α₂, δ, β and γ. The transmembrane α₁-subunit, for which there are 10 genes, is the largest subunit and incorporates the voltage sensor, conduction pore and gating apparatus. All other subunits have auxiliary roles and modulate the kinetics and current magnitude of the α₁-subunit. The α₂ and δ subunits are encoded by the same gene and are linked by a disulphide bond, with four α₂/δ genes identified in humans. Similarly, four genes have been identified for the cytoplasmic β-subunit, and eight genes identified for the γ-subunit. Multiple genes for each subunit and alternative splicing of each gene generates a high degree of heterogeneity within Ca_V channels.

Using pharmacological and electrophysiological techniques, at least six types of voltage-gated channels have been identified, grouped into three families depending on their sensitivity to different blockers, single-channel conductance and voltage-dependence. Ca_V1.x are high-voltage-activated, dihydropyridine-sensitive channels (L-type), Ca_V2.x are high-voltage-activated, dihydropyridine-insensitive channels (N-, P/Q- and R-types) and Ca_V3.x are low-voltage-activated, low conductance channels (T-type).