The Effects of κ-Opioid Receptor Stimulation on Electrical Coupling during Ischemia in the Perfused Isolated Rat Heart

Two series of experiments were performed in the perfused isolated rat heart to determine whether stimulation of kappa-opioid receptor with U50,488H, a selective kappa-opioid receptor agonist, produces any changes in electrical coupling during prolonged ischemia and whether these changes in electrical coupling is associated with the cardioprotection induced by U50,488H. It was found that U50,488H concentration dependently increased formazan content and reduced lactate dehydrogenase (LDH) release induced by 30 min of ischemia and 120 min of reperfusion, and the ameliorating effect of 10^-5 mol/L U50,488H was abolished by 5times10^-6 mol/L nor-binaltorphimine (nor-BNI), a selective kappa-opioid receptor antagonist, or 10^-4 mol/L 5-hydroxydecanoate (5-HD), a selective mitochondrial ATP-sensitive K⁺ (K_ATP) channels blocker. The onset of electrical uncoupling during prolonged ischemia was delayed by U50,488H, and delaying effect was not only abolished, but also advanced by nor-BNI or 5-HD compared with control group. These results demonstrate that delayed electrical uncoupling is associated with the cardioprotection induced by U50,488H. These effects of U50,488H are mediated by mitochondrial K_ATP channels