Simulation of action potentials from metabolically impaired cardiac myocytes: Role of ATP-sensitive K+ current

José M. Ferrero, Javier Sáiz, José M. Ferrero, Nitish V. Thakor

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)208-221
Number of pages14
JournalCirculation research
Volume79
Issue number2
DOIs
StatePublished - Jan 1 1996

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Keywords

  • ATP-regulated channels
  • K efflux
  • action potential shortening
  • computer model
  • myocardial ischemia

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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