Does restoration of action potential phase 1 repolarization improve Ca2+ release synchrony and reduce late Ca2+ spark rate in failing cardiac myocytes?
Restoring action potential phase 1 repolarization in failing cardiac myocytes improves calcium release synchrony and reduces arrhythmogenic late calcium sparks, offering a potential new mechanistic approach to prevent sudden cardiac death in heart failure.
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.
Fowler et al. (Wed,) studied this question.