Cardiac ion channels in health and disease

Cardiac electrical activity depends on the coordinated propagation of excitatory stimuli through the heart and, as a consequence, the generation of action potentials in individual cardiomyocytes. Action potential formation results from the opening and closing (gating) of ion channels that are expressed within the sarcolemma of cardiomyocytes. Ion channels possess distinct genetic, molecular, pharmacologic, and gating properties and exhibit dissimilar expression levels within different cardiac regions. By gating, ion channels permit ion currents across the sarcolemma, thereby creating the different phases of the action potential (e.g., resting phase, depolarization, repolarization). The importance of ion channels in maintaining normal heart rhythm is reflected by the increased incidence of arrhythmias in inherited diseases that are linked to mutations in genes encoding ion channels or their accessory proteins and in acquired diseases that are associated with changes in ion channel expression levels or gating properties. This review discusses ion channels that contribute to action potential formation in healthy hearts and their role in inherited and acquired diseases.