FIGURE 4.

Electrophysiologic instabilities in atrial myocytes. Early afterdepolarizations in hA-CMs exhibit the same essential mechanisms as occur in ventricular cells. (A) Phase-2 EADs result from the kinetic interaction of I_CaL and the outward potassium current involving multiple K⁺ channel species. In general, these events are uncovered during reduced repolarization reserve through I_CaL potentiation or K⁺ channel antagonists, particularly I_Kr inhibitors. (B) A second class of EADs occurs when repolarization is disrupted during phase 3 by forward mode Na⁺-Ca²⁺ exchange. This additional I_NCX is a secondary effect of dis-coordinated or simply exaggerated I_CaL-triggered SR Ca²⁺ release. Importantly these EADs generally recruit either I_CaL or I_Na as the major carrier of the inward current after I_NCX has sufficiently slowed late repolarization. (C) Finally, I_NCX is also responsible for initiating DADs secondary to spontaneous SR Ca²⁺ release during atrial diastole. Time scale for all panels is 0–1 s and voltage range from –80 to +40 mVs.