Voltage-gated calcium channels (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

Abstract

Calcium (Ca2+) channels are voltage-gated ion channels present in the membrane of most excitable cells. The nomenclature for Ca2+channels was proposed by [110] and approved by the NC-IUPHAR Subcommittee on Ca2+ channels [60]. Ca2+ channels form hetero-oligomeric complexes. The α1 subunit is pore-forming and provides the binding site(s) for practically all agonists and antagonists. The 10 cloned α1-subunits can be grouped into three families: (1) the high-voltage activated dihydropyridine-sensitive (L-type, CaV1.x) channels; (2) the high-voltage activated dihydropyridine-insensitive (CaV2.x) channels and (3) the low-voltage-activated (T-type, CaV3.x) channels. Each α1 subunit has four homologous repeats (I–IV), each repeat having six transmembrane domains and a pore-forming region between transmembrane domains S5 and S6. Gating is thought to be associated with the membrane-spanning S4 segment, which contains highly conserved positive charges. Many of the α1-subunit genes give rise to alternatively spliced products. At least for high-voltage activated channels, it is likely that native channels comprise co-assemblies of α1, β and α2–δ subunits. The γ subunits have not been proven to associate with channels other than the α1s skeletal muscle Cav1.1 channel. The α2–δ1 and α2–δ2 subunits bind gabapentin and pregabalin.