A DYNAMIC-MODEL OF THE CARDIAC VENTRICULAR ACTION-POTENTIAL .2. AFTERDEPOLARIZATIONS, TRIGGERED ACTIVITY, AND POTENTIATION

The action potential model presented in our accompanying article in this journal is used to investigate phenomena that involve dynamic changes of [Ca2+](i), as described below. Delayed afterdepolarizations (DADs) are induced by spontaneous Ca2+ release from the sarcoplasmic reticulum (SR), which, in turn, activates both the Na+-Ca2+ exchanger (I-NaCa) and a nonspecific Ca2+-activated current (I-ns(Ca)). The relative contributions of I-NaCa and of I-ns(Ca) to the generation of DADs are different under different degrees of Ca2+ overload. Early afterdepolarizations (EADs) can be categorized into two types: (1) plateau EADs, resulting from a secondary activation of the L-type Ca2+ current during the plateau of an action potential, and (2) phase-3 EADs, resulting from activation of I-NaCa and I-ns(Ca) by increased [Ca2+](i) due to spontaneous Ca2+ release from the SR during the late repolarization phase. Spontaneous rhythmic activity and triggered activity are caused by spontaneous Ca2+ release from the SR under conditions of Ca2+ overload. Postextrasystolic potentiation reflects the time delay associated with translocation of Ca2+ from network SR to junctional SR, The cell is paced at high frequencies to investigate the long-term effects on the intracellular ionic concentrations.