Arrhythmogenic late Ca <sup>2+</sup> sparks in failing heart cells and their control by action potential configuration
Ewan D. Fowler, Nan Wang, Melanie Hezzell, Guillaume Chanoit, Jules C. Hancox, Mark B. Cannell
Abstract
Significance Sudden cardiac death in heart failure is a major unsolved clinical problem that is linked to the development of a spontaneous arrhythmia. Early afterdepolarizations (EADs) are an arrhythmogenic mechanism, but the cellular trigger for EADs in heart failure is unclear. We show that the reduction in synchronous Ca 2+ release early in the action potential (AP) of failing cardiac myocytes promotes the appearance of late Ca 2+ sparks which can propagate, forming Ca 2+ ripples and waves. These, in turn, produce an inward sodium–calcium exchange current which opposes AP repolarization. Restoration of AP phase 1 repolarization improved Ca 2+ release synchrony and reduced late Ca 2+ spark rate, suggesting a different approach to reducing the risk of sudden death in heart failure.