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The L-type calcium channel alpha-1 subunit, specifically Cav1.2, is the principal pore-forming and voltage-sensing component of L-type voltage-gated calcium channels. These channels mediate Ca²⁺ influx into excitable cells in response to membrane depolarization, triggering muscle contraction, hormone secretion, and neuronal signaling. It is a large protein (~170–240 kDa) composed of four homologous domains (I–IV), each containing six transmembrane segments (S1–S6). The S4 segment acts as the voltage sensor, and the region between S5 and S6 forms the ion-selective pore. The channel complex includes auxiliary subunits (α₂δ, β, +/- γ) that modulate trafficking, gating kinetics, pharmacology, and surface expression. Cav1.2 channels mediate high-voltage activated (HVA) currents and are crucial for cardiac myocyte excitation-contraction coupling, smooth muscle contraction, neuronal dendritic signaling, and neuroendocrine regulation. L-type channels containing Cav1.2 are sensitive to dihydropyridine drugs (“DHP receptors”), phenylalkylamines, benzothiazepines and mutations or dysregulation can lead to various pathologies.
L-type calcium channel blockade
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