A role of opening of mitochondrial ATP-sensitive potassium channels in the infarct size-limiting effect of ischemic preconditioning via activation of protein kinase C in the canine heart

Abstract

The opening of mitochondrial ATP-sensitive K + (mitoK ATP) channels triggers or mediates the infarct size (IS)-limiting effect of ischemic preconditioning (IP). Because ecto-5′-nucleotidase related to IP is activated by PKC, we tested whether the opening of mitoK ATP channels activates PKC and contributes to either activation of ecto-5′-nucleotidase or IS-limiting effect. In dogs, IP procedure decreased IS and activated ecto-5′-nucleotidase, both of which were mimicked by transient exposure to either cromakalim or diazoxide, and these effects were blunted by either GF109203X (a PKC inhibitor) or 5-hydroxydecanoate (a mitoK ATP channel blocker), but not by HMR-1098 (a surface sarcolenmal K ATP channel blocker). Either cromakalim or diazoxide activated both PKC and ecto-5′-nucleotidase, which was blunted by either GF109203X or 5-hydroxydecanoate, but not by HMR-1098. We concluded that the opening of mitoK ATP channels contributes to either activation of ecto-5′-nucleotidase or the infarct size-limiting effect via activation of PKC in canine hearts.