Simulation study of action potentials from metabolically impaired cardiac myocytes

The aim of this work is to quantitatively study the role of the ATP-sensitive potassium current (I_K-ATP) and its contribution to the electrophysiological changes which occur during metabolic impairment in ventricular cardiac myocytes. For this purpose, we have formulated a model of the I_K-ATP current and incorporated it into the Luo-Rudy model of the ventricular cardiac action potential. We simulated action potentials (AP) developed by space-clamped myocytes under different intracellular levels of ATP and ADP. At normal ionic concentrations, only approx.0.6% of the channels, when open, accounted for a 50% reduction in AP duration. Increased levels of intracellular Mg²⁺ counteract this shortening, while high extracellular potassium has the opposite effect. Our theoretical results show that opening of I_K-ATP channels plays a significant role in AP shortening during hypoxic/ischemic episodes, with the fraction of open channels involved being very low (less than 1%).