alpha1C

Alpha1C, commonly referred to as the Cav1.2 alpha1 subunit, is the pore-forming component of the L-type voltage-gated calcium channel. It is encoded by the CACNA1C gene and assembles with auxiliary subunits such as beta and alpha2delta to form a functional channel that resides in the plasma membrane. The alpha1C subunit determines the channel’s conductance and voltage dependence, enabling calcium influx when the cell membrane is depolarized.

Cav1.2 channels are widely expressed, with high levels in the heart and brain, and are present in other tissues as well. The CACNA1C gene undergoes alternative splicing, producing multiple isoforms that can vary in tissue distribution and biophysical properties. The resulting calcium currents contribute to diverse physiological processes, including cardiac action potential plateau and excitation-contraction coupling, as well as neuronal activity, neurotransmitter release, and activity-dependent gene regulation.

Genetic and clinical significance: Rare mutations in CACNA1C cause Timothy syndrome, a multisystem disorder characterized by prolonged QT interval, syndactyly, and developmental anomalies, arising from impaired inactivation of Cav1.2 channels. Common genetic variants at CACNA1C have been associated with susceptibility to psychiatric conditions such as bipolar disorder and schizophrenia, though the mechanisms remain under investigation.

Pharmacology and regulation: Cav1.2 channels are targets of calcium channel blockers, including dihydropyridines (e.g., nifedipine), phenylalkylamines (e.g., verapamil), and benzothiazepines (e.g., diltiazem). Channel function is modulated by auxiliary subunits and signaling pathways, and regulation of Cav1.2 activity influences cardiac electrophysiology and neuronal calcium signaling.