Intracellular Ca2+ waves, afterdepolarizations, and triggered arrhythmias

Clinical studies have shown that sudden death is initiated by an ill-timed propagated ectopic beat that leads to fibrillation.1-4 However, the mechanism underlying these focal excitations is not completely understood. Experimental studies have demonstrated that abnormal calcium (Ca2+) cycling is a critical factor in the development of focal excitations.5-9 These excitations can be caused by spontaneous Ca2+ release (SCR) in the form of intracellular Ca2+ waves. These waves are initiated when Ca2+ release from a few Ca2+ release units (CRUs) on the sarcoplasmic reticulum (SR) causes regenerative release in adjoining units via Ca2+-induced Ca2+ release (CICR), causing Ca2+ wave propagation. The resulting depolarizing inward current through the electrogenic Na+-Ca2+ exchanger (NCX) depolarizes the cell.