Dissecting the roles of calcium cycling and its coupling with voltage in the genesis of early afterdepolarizations in cardiac myocyte models

• DOI: 10.1371/journal.pcbi.1011930
• Publication Date: 2024-02-28T18:37:35Z
• Authors: Rui Wang; Zhilin Qu; Xiaodong Huang
• Keywords: Afterdepolarization; Cardiac action potential; Calcium Signaling

Early afterdepolarizations (EADs) are abnormal depolarizations during the plateau phase of action potential, which known to be associated with lethal arrhythmias in heart. There two major hypotheses for EAD genesis based on experimental observations, i.e., voltage ( V m )-driven and intracellular calcium (Ca)-driven mechanisms. In ventricular myocytes, Ca bidirectionally coupled, can affect each other’s dynamics result new dynamics, however, roles cycling its coupling EADs have not been well understood. this study, we use an potential model that is capable independent oscillations investigate genesis. Four different mechanisms identified, either driven by or alone, caused their interactions. We also 5 other models assess these show mainly -driven. These mechanistic insights from our simulations provide a theoretical base understanding experimentally observed EAD-related arrhythmogenesis.