Direct preconditioning of cardiac myocytes via opioid receptors and K-ATP channels

Previous studies demonstrated that opioid receptor activation mimics the ca rdioprotective effect of ischemic preconditioning via K-ATP, channels in th e intact heart. However, it is unknown whether this beneficial effect is ex erted at tl;the level of the cardiac myocyte or coronary vasculature or is mediated via the sarcolemmal or the mitochondrial K-ATP channel. Thus, the purpose of the present study was to investigate whether opioid receptor sti mulation could mimic the cardioprotective effect of preconditioning in a ca rdiac myocyte model of simulated ischemia. Cardiac ventricular myocytes cul tured from chick embryos 14 days in ovo were used as an in vitro model for ischemic preconditioning, A 5-minute exposure of the myocytes to the opioid receptor agonist morphine protected the myocytes during. subsequent 90-min ute period of simulated ischemia, which was manifested as a pronounced redu ction in the percentage of cardiac cells killed and the amount of creatine kinase released during ischemia, The preconditioning;preconditioning-like e ffect of morphine was concentration-dependent, reached a maximal effect at 1 mu mol/L, and was-reversed by naloxone(0.1 to 10 mu mol/L). When K-ATP, c hannel antagonists,such as glibenclamide, or the mitochondrial selective in hibitor 5-hydroxydecanoic acid were present during preexposure to morphine, they abolished the protective effect of morphine. Thus, cardiac myocytes e xpress functional opioid receptors, and their activation mimics the cardiop rotective effect of ischemic preconditioning. These results provide direct evidence that the preconditioning-like effect of morphine in the intact hea rt can be exerted at the level of cardiac myocytes and is most likely the r esult of mitochondrial K-ATP channel activation.