Rational strategy to stop arrhythmias: Early afterdepolarizations and L-type Ca2+ current

Unlike the brief action potentials (APs) in skeletal myocytes or neurons, the human cardiac AP takes 100s of milliseconds to repolarize the cell. This slow repolarization is essential for proper excitation–contraction coupling in cardiac muscle, and precise control of AP duration contributes to electrical stability. Under various pathological conditions, often when the AP duration is prolonged, repolarization can transiently fail with a sudden transient depolarization of membrane potential (Fig. 1). If such an early afterdepolarization (EAD) reaches threshold, it can trigger a premature AP and thereby initiate potentially fatal ventricular arrhythmias such as torsades de pointes (TdP) and ventricular fibrillation (Cranefield and Aronson, 1991). Thus, understanding the causes of EADs and how one might block them is of significant clinical importance.