Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1C gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin-GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA). Calcium channels containing the alpha-1C subunit play an important role in excitation-contraction coupling in the heart. The various isoforms display marked differences in the sensitivity to DHP compounds. Binding of calmodulin or CABP1 at the same regulatory sites results in an opposit effects on the channel function.
Expressed in brain, heart, jejunum, ovary, pancreatic beta-cells and vascular smooth muscle. Overall expression is reduced in atherosclerotic vascular smooth muscle.
Involvement in disease
Timothy syndrome Brugada syndrome 3
Belongs to the calcium channel alpha-1 subunit (TC 1.A.1.11) family. CACNA1C subfamily.
Each of the four internal repeats contains five hydrophobic transmembrane segments (S1, S2, S3, S5, S6) and one positively charged transmembrane segment (S4). S4 segments probably represent the voltage-sensor and are characterized by a series of positively charged amino acids at every third position. Binding of intracellular calcium through the EF-hand motif inhibits the opening of the channel.
Phosphorylation by PKA activates the channel.
Membrane. Cell membrane. The interaction between RRAD and CACNB2 regulates its trafficking to the cell membrane.