title: Simulation of action potentials from metabolically impaired cardiac myocytes. Role of ATP-sensitive K+ current.
abstract: The role of the ATP-sensitive K+ current (IK-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 IK-ATP is formulated and incorporated into the Luo-Rudy ionic model of the ventricular action potential. Action potentials under different degrees of activation of IK-ATP are simulated. Our results show that in normal ionic concentrations, only approximately 0.6% of the KATP 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+]0, such as those found in early ischemia, the activation of only approximately 0.4% of the KATP channels could account for a 50% reduction in action potential duration. Thus, our results suggest that opening of IK-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 IK-ATP alone does not quantitatively account for the observed K+ efflux in metabolically impaired cardiac myocytes. Mechanisms other than KATP channel activation should be responsible for a significant part of the K+ efflux measured in hypoxic/ischemic situations.
authors: Laboratorio Integrado de Bioingeniería, Universidad Politécnica de Valencia, Spain. cferrero@pleiades.upv.es
authors: J M
authors: JM
authors: Ferrero
authors: J
authors: J
authors: Sáiz
authors: J M
authors: JM
authors: Ferrero
authors: N V
authors: NV
authors: Thakor
mesh_terms: D000200:Action Potentials; D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D003198:Computer Simulation; D004594:Electrophysiology; D005110:Extracellular Space / Q000378:metabolism; D006801:Humans; D008274:Magnesium / Q000378:metabolism; D008955:Models, Cardiovascular; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000502:physiology*; D012964:Sodium / Q000378:metabolism
chemical_list: D015221:Potassium Channels; D000255:Adenosine Triphosphate; D012964:Sodium; D008274:Magnesium; D011188:Potassium