AJP - Heart and Circulatory Physiology, Vol 267, Issue 5 1888-H1894, Copyright © 1994 by American Physiological Society

ARTICLES

Activation of ATP-sensitive potassium channels lowers threshold for ischemic preconditioning in dogs

Z. Yao and G. J. Gross
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee 53226.

The purpose of the present study was to determine whether enhanced activation of myocardial ATP-dependent potassium channels (KATP) with a potassium channel opener, bimakalim, can reduce the time necessary to produce the protective effect of ischemic preconditioning and to determine whether this effect is mediated via accelerating the rate of action potential shortening during preconditioning. Barbital-anesthetized dogs were subjected to 60 min of left anterior descending coronary artery (LAD) occlusion followed by 4 h of reperfusion. Ten minutes of preconditioning was found to markedly reduce myocardial infarct size from 30.6 +/- 4.7 to 7.1 +/- 2.6%. Subsequently, it was observed that either 3 min of LAD occlusion or a 3-min intracoronary infusion with 0.3 micrograms/min of bimakalim did not reduce myocardial infarct size. However, intracoronary infusion with bimakalim during the 3-min preconditioning period markedly reduced myocardial infarct size to a similar extent as that of ischemic preconditioning (12.2 +/- 1.9%). In addition, it was observed that bimakalim markedly accelerated the ischemia-induced shortening of the action potential during preconditioning. These results are the first to demonstrate that activation of KATP channels with a potassium channel opener reduces the threshold of time necessary to produce preconditioning in anesthetized dogs. These data also suggest that KATP channel activation may produce this effect by enhancing the rate of ischemic myocardial action potential shortening during preconditioning.

This article has been cited by other articles:

				G. J. Gross and J. N. Peart KATP channels and myocardial preconditioning: an update Am J Physiol Heart Circ Physiol, August 7, 2003; 285(3): H921 - H930. [Abstract] [Full Text] [PDF]

				J. M. Nerbonne, C. G. Nichols, T. L. Schwarz, and D. Escande Genetic Manipulation of Cardiac K+ Channel Function in Mice: What Have We Learned, and Where Do We Go From Here? Circ. Res., November 23, 2001; 89(11): 944 - 956. [Abstract] [Full Text] [PDF]

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				G. J. Gross and R. M. Fryer Sarcolemmal Versus Mitochondrial ATP-Sensitive K+ Channels and Myocardial Preconditioning Circ. Res., May 14, 1999; 84(9): 973 - 979. [Abstract] [Full Text] [PDF]

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