Opening of mitochondrial KATP channel occurs downstream of PKC-ε activation in the mechanism of preconditioning

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Abstract
We examined whether the mitochondrial ATP-sensitive K channel (KATP) is an effector downstream of protein kinase C-ε (PKC-ε) in the mechanism of preconditioning (PC) in isolated rabbit hearts. PC with two cycles of 5-min ischemia/5-min reperfusion before 30-min global ischemia reduced infarction from 50.3 ± 6.8% of the left ventricle to 20.3 ± 3.7%. PC significantly increased PKC-ε protein in the particulate fraction from 51 ± 4% of the total to 60 ± 4%, whereas no translocation was observed for PKC-δ and PKC-α. In mitochondria separated from the other particulate fractions, PC increased the PKC-ε level by 50%. Infusion of 5-hydroxydecanoate (5-HD), a mitochondrial KATP blocker, after PC abolished the cardioprotection of PC, whereas PKC-ε translocation by PC was not interfered with 5-HD. Diazoxide, a mitochondrial KATP opener, infused 10 min before ischemia limited infarct size to 5.2 ± 1.4%, but this agent neither translocated PKC-ε by itself nor accelerated PKC-ε translocation after ischemia. Together with the results of earlier studies showing mitochondrial KATP opening by PKC, the present results suggest that mitochondrial KATP-mediated cardioprotection occurs subsequent to PKC-ε activation by PC.

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