ATP-SENSITIVE K- AN ENDOGENOUS MECHANISM FOR PROTECTION OF THE HEART(CHANNELS IN CARDIAC ISCHEMIA )

The Role of ATP-sensitive K+ channels (K(ATP)) in action potential sho rtening and protection of myocardium in ischemia were explored using i solated ventricular myocytes and arterially perfused right ventricular walls of guinea pigs. Conditions ''simulating'' some aspects of ische mia-(10.8 mM K0+, 6.9 pH0, 20 mM lactate, no glucose; 10 mM 2-deoxy-D- glucose; and either 1 mM cyanide or no O2 (bubbled with 95/5% N2/CO2)- caused a decline in action potential duration (APD) and the elaboratio n of time- and voltage-independent, steady-state outward conductance d ue to K(ATP), which could be inhibited with glibenclamide (50 muM) in myocytes studied via the perforated patch (nystatin) whole-cell techni que. Right ventricular walls subjected to no-flow ischemia +/- glibenc lamide (10 muM) to block, or +/- pinacidil (1 and 10 muM) to activate, K(ATP), respectively, exhibited varied ischemic injury. Glibenclamide caused a greater fall in resting membrane potential, inhibited the de cline in APD, caused an early rise in resting tension, and inhibited r ecovery of contractile function upon reflow. Pinacidil caused a greate r decline in APD, inhibited changes in resting tension, and improved r ecovery during reperfusion. These results indicate that K(ATP) contrib utes to action potential shortening in isolated myocytes in simulated ischemia and intact myocardium in no-flow ischemia. Activation of this membrane current may be an important adaptive mechanism for protectin g the myocardium when blood flow to the tissue is compromised.