SIMULATION OF ACTION-POTENTIALS FROM METABOLICALLY IMPAIRED CARDIAC MYOCYTES - ROLE OF ATP-SENSITIVE K+ CURRENT

The role of the ATP-sensitive K+ current (I-K-ATP) and its contributio n to electrophysiological changes that occur during metabolic impairme nt in cardiac ventricular myocytes is still being discussed. The aim o f this work was to quantitatively study this issue by using computer m odeling. A model of I-K-ATP is formulated and incorporated into the Lu o-Rudy ionic model of the ventricular action potential. Action potenti als under different degrees of activation of I-K-ATP are simulated. Ou r results show that in normal ionic concentrations, only approximate t o 0.6% of the K-ATP channels, when open, should account for a 50% redu ction in action potential duration. However, increased levels of intra cellular Mg2+ counteract this shortening. Under conditions of high [K](o), such as those found in early ischemia, the activation of only ap proximate to 0.4% of the K-ATP channels could account for a 50% reduct ion in action potential duration. Thus, our results suggest that openi ng of I-K-ATP channels should play a significant role in action potent ial shortening during hypoxic/ischemic episodes, with the fraction of open channels involved being very low (<1%). However, the results of t he model suggest that activation of I-K-ATP alone does not quantitativ ely account for the observed K+ efflux in metabolically impaired cardi ac myocytes. Mechanisms other than K-ATP channel activation should be responsible for a significant part of the K+ efflux measured in hypoxi c/ischemic situations.