The mitochondrial Ca(2+)-activated K(+) channel contributes to cardioprotection by limb remote ischemic preconditioning in rat.

AIMS

To investigate the role of the mitochondrial Ca(2+)-activated K(+) channel in cardioprotection induced by limb remote ischemic preconditioning.

MAIN METHODS

Male Sprague-Dawley rats (250-300 g) were randomized into control, ischemia/reperfusion (I/R), remote ischemic preconditioning (RPC), NS1619 (a specific mitochondrial Ca(2+)-activated K(+) channel opener), and RPC+paxilline (a specific mitochondrial Ca(2+)-activated K(+) channel inhibitor) groups. RPC was induced by 4 cycles of 5 min of ligation followed by 5 min of reperfusion of the left femoral artery. Myocardial I/R was achieved by ligation of the left anterior descending coronary artery for 30 min, followed by 120 min of reperfusion. Infarct size was determined by 2,3,5-triphenyltetrazolium chloride staining, the hemodynamics were monitored, and lactate dehydrogenase (LDH) levels in the coronary effluent, manganese superoxide dismutase (Mn-SOD) content in mitochondria and mitochondrial membrane potential were measured spectrophotometrically. The ultrastructure of cardiomyocyte mitochondria was assessed by electron microscopy.

KEY FINDINGS

NS1619 (10 μM) improved heart function, decreased infarct size, reduced LDH release, maintained mitochondrial structural integrity and mitochondrial membrane potential, and increased the mitochondrial content of Mn-SOD to the same degree as RPC treatment. However, paxilline (1 μM) eliminated the cardioprotective effect conferred by RPC.

SIGNIFICANCE

The mitochondrial Ca(2+)-activated K(+) channel participates in the myocardial protection by limb remote ischemic preconditioning.