ATP-sensitive K+ channels in cardiac ischemia: an endogenous mechanism for protection of the heart.
The Role of ATP-sensitive K+ channels (KATP) in action potential shortening and protection of myocardium in ischemia were explored using isolated ventricular myocytes and arterially perfused right ventricular walls of guinea pigs. Conditions "simulating" some aspects of ischemia--(10.8 mM K+o, 6.9 pHo, 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 elaboration of time- and voltage-independent, steady-state outward conductance due to KATP, which could be inhibited with glibenclamide (50 microM) in myocytes studied via the perforated patch (nystatin) whole-cell technique. Right ventricular walls subjected to no-flow ischemia +/- glibenclamide (10 microM) to block, or +/- pinacidil (1 and 10 microM) to activate, KATP, respectively, exhibited varied ischemic injury. Glibenclamide caused a greater fall in resting membrane potential, inhibited the decline in APD, caused an early rise in resting tension, and inhibited recovery of contractile function upon reflow. Pinacidil caused a greater decline in APD, inhibited changes in resting tension, and improved recovery during reperfusion. These results indicate that KATP contributes 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 protecting the myocardium when blood flow to the tissue is compromised.
Cole
W C
WC
Department of Physiology, University of Manitoba, Winnipeg, Canada.
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D004594:Electrophysiology; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000166:cytology; D066298:In Vitro Techniques; D017202:Myocardial Ischemia / Q000503:physiopathology*; D015221:Potassium Channels / Q000502:physiology*; D015427:Reperfusion Injury / Q000503:physiopathology; D016276:Ventricular Function
D015221:Potassium Channels; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate