MEND occurs in cardiac myocytes without preceding exocytic responses and can be induced by spontaneous cycles of Ca release. (A) Rat cardiac myocyte with 6 mM of cytoplasmic ATP. MEND develops rapidly during activation of NCX1 and continues for several seconds after terminating Ca influx as cells continued to contract spontaneously. MEND reversal in myocytes is labile, becoming substantially slower from one MEND cycle to the next. Reversal was negligible when MEND was allowed to proceed to a final loss of >30% of the cell surface. (B–D) Different patterns of MEND responses observed in mouse cardiac myocytes. (B) Mouse myocyte with contraction blocked by 17 µM blebbistatin. Na/Ca exchange current is relatively large. MEND begins within 3 s of activating Ca influx, and MEND terminates when exchange current is deactivated. (C) Mouse myocyte without blebbistatin. Brief activation of reverse exchange current promotes spontaneous cycles of Ca release, accompanied by transient current changes that are evident in the current record. MEND begins with no exocytic response and terminates spontaneously as spontaneous contractile activity terminates. (D) Mouse myocyte without blebbistatin. Exchange current is negligibly small. The application of Ca activates spontaneous cycles of Ca release accompanied by transient current changes. MEND begins after extracellular Ca has been removed and during spontaneous contractile activity, and it terminates spontaneously with no evident relationship to the termination of spontaneous activity. The bright field record of this experiment is provided as Video 3.