Aberrant Zn homeostasis is associated with dysregulated intracellular Ca release， resulting in chronic heart failure. In the failing heart a small population of cardiac ryanodine receptors (RyR2) displays sub-conductance-state gating leading to Ca leakage from sarcoplasmic reticulum (SR) stores， which impairs cardiac contractility. Previous evidence suggests contribution of RyR2-independent Ca leakage through an uncharacterized mechanism. We sought to examine the role of Zn in shaping intracellular Ca release in cardiac muscle. Cardiac SR vesicles prepared from sheep or mouse ventricular tissue were incorporated into phospholipid bilayers under voltage-clamp conditions， and the direct action of Zn on RyR2 channel function was examined. Under diastolic conditions， the addition of pathophysiological concentrations of Zn (≥2 nm) caused dysregulated RyR2-channel openings. Our data also revealed that RyR2 channels are not the only SR Ca-permeable channels regulated by Zn Elevating the cytosolic Zn concentration to 1 nm increased the activity of the transmembrane protein mitsugumin 23 (MG23). The current amplitude of the MG23 full-open state was consistent with that previously reported for RyR2 sub-conductance gating， suggesting that in heart failure in which Zn levels are elevated， RyR2 channels do not gate in a sub-conductance state， but rather MG23-gating becomes more apparent. We also show that in H9C2 cells exposed to ischemic conditions， intracellular Zn levels are elevated， coinciding with increased MG23 expression. In conclusion， these data suggest that dysregulated Zn homeostasis alters the function of both RyR2 and MG23 and that both ion channels play a key role in diastolic SR Ca leakage.