Integrated mechanisms of K+ loss in myocardial ischemia: a simulation study

During the early phase of myocardial ischemia, extracellular K⁺ accumulation is considered pivotal in the genesis of reentrant arrhythmias. Despite the importance of this phenomenon, the causes of cellular K⁺ loss are still unknown. Because of their ability to simulate the electrical activity of cardiomyocytes, action potential (AP) models provide an alternative for exploring their behavior under normoxic or pathological conditions. Our goal was to investigate, with the aid of computer simulations, the mechanisms responsible for the ischemic increase of extracellular K⁺ concentration ([K⁺]_o). The electrophysiological behavior of one single cardiomyocyte has been simulated during 14 minutes in the absence of coronary flow, using a modified version of Luo Rudy phase II AP model. The activation of the ATP-sensitive K⁺ current, as well as other possible causes of the ischemic increase of [K⁺]_o such as inhibition of Na⁺/K⁺ pump current and altered Na⁺ fluxes, have been taken into account in the simulations. Our results show that the concomitant effect of these three mechanisms in the absence of coronary flow leads to an increase of [K⁺]_o quantitative and qualitatively similar to the experimentally observed during acute myocardial ischemia.