Calcium channel, voltage-dependent, L type, alpha 1C subunit (Cav1.2)

The Calcium channel, voltage-dependent, L type, alpha 1C subunit (Cav1.2) is a critical transmembrane protein and voltage-gated ion channel. As the main alpha-1 subunit of L-type calcium channels in the adult heart, it forms the pore responsible for mediating the influx of calcium ions (Ca²⁺) into the cell upon membrane depolarization. The alpha-1 subunit consists of 24 transmembrane segments and forms a complex with alpha-2/delta and beta subunits in a 1:1:1 ratio. Its structure includes a voltage sensing domain (formed by S1-S4 segments) and a conduction pore (formed by S5-S6 segments), as well as gating apparatus. Cav1.2 plays crucial roles in signal transduction, membrane depolarization, action potential regulation, and particularly excitation-contraction coupling in cardiac, skeletal, and smooth muscle, as well as calcium-induced calcium release from endoplasmic reticulum stores. It is widely expressed in tissues including cardiac tissue, smooth muscle, neurons, pancreatic cells, and fibroblasts. Regulation involves voltage-dependent mechanisms, inhibition by STIM1, and binding of Ca²⁺/calmodulin to the C-terminus. Mutations in the gene encoding this subunit (CACNA1C) are associated with severe disorders like Timothy Syndrome (TS1, TS2) and Long QT Syndrome type 8 (LQT8), leading to cardiac arrhythmias and other developmental abnormalities. As a key ion channel, Cav1.2 is considered a therapeutic target, modulated by drugs such as dihydropyridines, which typically inhibit calcium influx by binding to the channel and affecting its gating kinetics.

Other names

CACNA1CL-type calcium channel alpha-1C subunitVoltage-dependent L-type calcium channel subunit alpha-1CAlpha-1C subunit of voltage-dependent calcium channel

Inhibition of calcium influx through binding to and inhibiting the channel. Modulation of channel gating kinetics. Drugs targeting this channel typically work by blocking calcium ion influx, which can reduce muscle contraction and electrical excitability.