Mitochondrial Ca 2+ ‐Dependent Big K + Channels in Postconditioning of Guinea Pig Isolated Hearts

Abstract

Ca2+ -dependent “Big” conductance K+ (mBKCa) channels are believed to exist in inner mitochondrial (m) membranes of guinea pig myocytes. Our aim was to explore if cardiac post-conditioning (intervention to mitigate injury immediately after ischemia), could be mediated by activation of mBKCa channels by NS1619. Guinea pig isolated hearts (n=20) were subjected to 30 min of global ischemia and 120 min of reperfusion (RP). Groups were: untreated (CON) and Post-conditioning (PostC). PostC hearts were perfused with 3 μM NS1619 for the first 10 min on RP. Developed pressure (LVP, mmHg) was recorded along with a spectrofluorometric on-line measure of myocardial superoxide (O2·−), using dihydroethidium. Infarct size was measured by the TTC method. ANOVA (mean±sem; *PostC vs. CON, p <0.05). At 60 min RP LVP was higher after PC (43±4*) than in CON (29±5) groups. O2·− detected was lower after PostC (1.92±0.06*) than in CON (2.06±0.06). Infarct size at 120 min RP was lower after PostC (33±4*) than in CON (46±4). Post-conditioning with NS1619 protects against RP injury as shown by improved myocardial contractility, reduced generation of O2·− after ischemia and lower infarct size. Activation of the mBKCa channel immediately on RP may post-condition the heart by a mechanism that reduces release of O2·− at the mitochondrial electron transport chain secondary to improved mitochondrial bioenergetics.