Intermittent Early Afterdepolarizations Caused by Bistability

Early afterdepolarization (EAD) is one of the main triggers for cardiac arrhythmias. The intracellular sodium concentration ([Na]i) is critical in regulating both intracellular calcium (Ca) homeostasis and membrane voltage (V). However, the role of [Na]i in the formation of early afterdepolarizations (EADs) is not completely understood. In this study, we applied mathematical modeling to show that slow [Na]i accumulation can lead to a novel form of aperiodic voltage dynamics where a sequence of action potentials (APs) with EADs occurs intermittently during regular periodic pacing.