Mechanisms of triggered arrhythmias

Triggered activity in cardiac tissue is caused by afterdepolarizations. These are transient depolarizations of the cell membrane that occur before an action potential has fully repolarized (early afterdepolarizations; EADs) or after its complete repolarization (delayed afterdepolarizations; DADs). In recent years, much new information has been discovered about the mechanisms that cause EADs and DADs. DADs arise in Ca2+-loaded cells and result from an oscillatory increase of intracellular Ca2+ from focal regions of the sarcoplasmic reticulum, thereby activating a Ca2+-sensitive transient inward current. In contrast, EADS, at least those arising near the plateau, result from the interplay of surface membrane currents, and do not depend on Ca2+ overload. Lengthening of the action potential duration appears to lead to the time- and voltage-dependent recovery of L-type Ca2+ current to carry the depolarizing charge for this EAD. The mechanism causing a second type of EAD, the phase 3 EAD, remains to be explained. In this report, the cellular mechanisms thought to underlie the different types of triggered activity and their possible roles in generation of triggered arrhythmias are considered.