Ventricular ion channels and arrhythmias: an overview of physiology, pathophysiology and pharmacology

Abstract

Cardiac ion channels are critical transmembrane proteins that mediate almost all aspects of cardiac function including generation and propagation of cardiac action potential (AP) as well as maintenance of normal heart excitability and contraction. In addition, the pivotal role of cardiac ion channels in cardiac health and disease is underscored by the profound effects of their dysfunctional mutations on various arrhythmias. Hence, ion channels are vital targets for antiarrhythmic drugs. In this review, we first summarize the characteristics, structure of the various cardiac ion channels and their specific roles in cardiac electrophysiology. Subsequently, we highlight the implications of genetic mutations that disrupt ion channel function, which are associated with inherited cardiac arrhythmias. Finally, we address antiarrhythmic drugs acting on cardiac ion channels respectively, according to their therapeutic targets. In conclusion, this manuscript aims to review the physiology, pathophysiology and pharmacology of the most prominent ventricular NaV, CaV, KV, and Kir ion channels.