Voltage-dependent L-type and T-type calcium channels (Cav1.2, Cav3.1, Cav3.2)

Cardiac voltage-gated calcium channels, specifically the L-type (Cav1.2) and T-type (Cav3.1 and Cav3.2) isoforms, are essential for the electrical and mechanical activity of the heart [1, 5]. L-type channels are the primary source of calcium influx for excitation-contraction coupling in cardiomyocytes and are responsible for the plateau phase of the cardiac action potential [4, 7]. T-type channels activate at more negative membrane potentials and contribute significantly to the pacemaking activity of the sinoatrial node and conduction through the atrioventricular node [1, 20]. In pathological conditions such as heart failure and cardiac hypertrophy, T-type channels are often re-expressed in ventricular myocytes, contributing to arrhythmogenesis and remodeling [5, 11]. These channels are major therapeutic targets for treating hypertension, angina pectoris, and supraventricular arrhythmias [1, 12]. Traditional calcium channel blockers like nifedipine and verapamil primarily target L-type channels to induce vasodilation and reduce heart rate [9, 10]. Newer dual L- and T-type blockers, such as efonidipine, provide additional benefits by reducing heart rate and aldosterone secretion without triggering reflex tachycardia [3, 15]. Safety concerns associated with these drugs include excessive hypotension, bradycardia, and peripheral edema [10, 17].

Other names

Cav1.2Cav3.1Cav3.2CACNA1CCACNA1GCACNA1HL-type calcium channelT-type calcium channelDHP receptorLow-voltage activated calcium channel

Inhibition of voltage-gated calcium influx through the alpha-1 pore-forming subunit, leading to reduced intracellular calcium levels, vascular smooth muscle relaxation, and decreased cardiac contractility and conduction velocity.