Protein kinase C-dependent activation of K-ATP channel enhances adenosine-induced cardioprotection

Prior activation of protein kinase C (PKC) can precondition the cardiac cel l against injury during subsequent ischaemia. By using cultured chick ventr icular cell model for simulated ischaemia and preconditioning, the present study investigated the biochemical mechanism underlying the PKC-mediated pr econditioning. A 5 min exposure to PMA enhanced the ability of pinacidil to mediate cardioprotection during a subsequent 90 min period of ischaemia, w hich is consistent with a sustained activation of the K-ATP channel initiat ed by PKC, The brief prior exposure to PMA was also associated with an enha nced ability of the adenosine A(1) or A(3) receptor agonist 2-chloro-N-6-cy clopentyladenosine or N-6-(3-iodobenzyl)adenosine-5'-N-methyluronamide to e licit a cardioprotective response during the subsequent ischaemia. In myocy tes pretreated with PMA, the cardioprotection mediated by receptor agonist was blocked by the concomitant presence of K-ATP-channel antagonists gliben clamide or 5-hydroxydecanoic acid during the ischaemia. Thus the K-ATP chan nel acts downstream of the adenosine A, and A, receptors in mediating the p rotective effect due to prior PMA exposure. K-ATP channel activation is res ponsible for the adenosine receptor-mediated effect. PMA treatment had no e ffect on other A(1) or A(3) receptor-mediated effects such as the inhibitio n of adenylate cyclase, ruling out a direct stimulation of the receptor or G-protein by PMA, The present results indicate that prior stimulation of PK C causes a sustained K-ATP channel activation, which in turn renders the my ocyte more responsive to the protective action of adenosine A, and A, recep tor agonists during the subsequent ischaemia.