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(Circulation Research. 1996;79:208-221.)
© 1996 American Heart Association, Inc.

Articles

Simulation of Action Potentials From Metabolically Impaired Cardiac Myocytes

Role of ATP-Sensitive K⁺ Current

Jose M. Ferrero, Jr, Javier Saiz, Jose M. Ferrero, Nitish V. Thakor

the Laboratorio Integrado de Bioingenieria (J.M.F. Jr, J.S., J.M.F.), Departamento de Ingenieria Electronica, Universidad Politecnica de Valencia, Valencia, Spain, and the Department of Biomedical Engineering (J.M.F. Jr, J.S., N.V.T.), The Johns Hopkins University, Baltimore, Md.

The role of the ATP-sensitive K⁺ current (I_K-ATP) and its contribution to electrophysiological changes that occur during metabolic impairment in cardiac ventricular myocytes is still being discussed. The aim of this work was to quantitatively study this issue by using computer modeling. A model of I_K-ATP is formulated and incorporated into the Luo-Rudy ionic model of the ventricular action potential. Action potentials under different degrees of activation of I_K-ATP are simulated. Our results show that in normal ionic concentrations, only 0.6% of the K_ATP channels, when open, should account for a 50% reduction in action potential duration. However, increased levels of intracellular Mg²⁺ counteract this shortening. Under conditions of high [K⁺]_o, such as those found in early ischemia, the activation of only 0.4% of the K_ATP channels could account for a 50% reduction in action potential duration. Thus, our results suggest that opening of I_K-ATP channels should play a significant role in action potential shortening during hypoxic/ischemic episodes, with the fraction of open channels involved being very low (<1%). However, the results of the model suggest that activation of I_K-ATP alone does not quantitatively account for the observed K⁺ efflux in metabolically impaired cardiac myocytes. Mechanisms other than K_ATP channel activation should be responsible for a significant part of the K⁺ efflux measured in hypoxic/ischemic situations.

Key Words: computer model • ATP-regulated channels • myocardial ischemia • action potential shortening • K⁺ efflux

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