Sarcoplasmic reticulum calcium leak and its role in cardiac dysfunction

Sarcoplasmic reticulum (SR) Ca2+ leak is defined as SR Ca2+ release other than that during the active excitation-contraction coupling process, which includes Ca2+ sparks and waves as well as smaller Ca2+ events. SR Ca2+ leak can reduce SR Ca2+ available for release, causing systolic dysfunction and elevate diastolic ［Ca2+］i, contributing to diastolic dysfunction and arrhythmias. Moreover, SR Ca2+ leak is energetically costly because of the extra ATP used to re-pump Ca2+, leading to further deterioration of RyR2-related heart diseases such as arrhythmias and heart failure.