Pathophysiology of Ca_v1.3 L-type calcium channels in the heart

Ca²⁺ plays a crucial role in excitation-contraction coupling in cardiac myocytes. Dysfunctional Ca²⁺ regulation alters the force of contraction and causes cardiac arrhythmias. Ca²⁺ entry into cardiomyocytes is mediated mainly through L-type Ca²⁺ channels, leading to the subsequent Ca²⁺ release from the sarcoplasmic reticulum. L-type Ca²⁺ channels are composed of the conventional Ca_v1.2, ubiquitously expressed in all heart chambers, and the developmentally regulated Ca_v1.3, exclusively expressed in the atria, sinoatrial node, and atrioventricular node in the adult heart. As such, Ca_v1.3 is implicated in the pathogenesis of sinoatrial and atrioventricular node dysfunction as well as atrial fibrillation. More recently, Ca_v1.3 de novo expression was suggested in heart failure. Here, we review the functional role, expression levels, and regulation of Ca_v1.3 in the heart, including in the context of cardiac diseases. We believe that the elucidation of the functional and molecular pathways regulating Ca_v1.3 in the heart will assist in developing novel targeted therapeutic interventions for the aforementioned arrhythmias.