Abstract:

Objective    To investigate the roles of mitochondrial calcium-activated potassium channel (MitoKCa) and mitochondrial ATP-sensitive potassium channel (MitoKATP) in myocardial protection by limb remote preconditioning (RPC). Methods     Seventy-two Male Sprague Dawley rats were divided into nine groups( eight per group): ischemia reperfusion group（I/R）, RPC group, MitoKATP-channel opener group （diazoxide, DZ）, MitoKCa-channel opener group （NS1619）, MitoKCa inhibitor group （RPC+paxilline）, MitoKATP inhibitor group（RPC+5-HD）, RPC+NS1619+5-HD group, RPC+paxilline+DZ group and RPC+paxilline+5-HD group. Preparation of RPC model was made by the ligation of rat femoral artery for 5min followed by 5min reperfusion. The procedures was repeated for 4 times; Preparation of I/R model was made by the ligation of anterior descending coronary artery for 30min followed by 120min reperfusion. Heart hemodynamics of each group was measured. Size of myocardium infarction was measured by TTC staining method and the content of LDH in the effusion from coronary artery was detected spectrophotometrically. Results     Compared to I/R group, administration of NS1619(10μmol/L) and DZ(50μmol/L) both improved heart function, decreased myocardium infarction and restrained the release of LDH (P<0.01), which were similar to the remote ischemic preconditioning(RPC) group (P>0.05). However, no difference was observed when compared with RPC group (P>0.05). Administration of paxilline (1μmol/L) or 5HD (100μmol/L) abolished the protective effect of RPC (P<0.01). When one of the two (MitoKCa and MitoKATP) channels was blocked while the other was activated, cardiac protection was still observed. And there was no significant difference when compared to RPC group (P>0.05). When both channels was inhibited by the corresponding inhibitors at the same time, aggravated heart injury was noted compared to the situations in which only one of the two was blocked (P<0.01). Conclusion     Opening of both MitoKCa and MitoKATP channels participates in the myocardial protection in limb remote ischemic preconditioning. They may work in independent but cooperative ways.

Key words: Remote preconditioning; Mitochondrial calcium-activated potassium channel; Heart；Ischemia/reperfusion