Mechanistic investigation of the causes of cellular K/sup +/ loss during acute myocardial ischemia: a simulation study

During acute myocardial ischemia, extra-cellular K/sup +/ accumulation has been proved to induce re-entrant arrhythmias. Despite the important of this phenomenon, the causes of cellular K/sup +/ loss remain still unknown. We investigated the simultaneous effect of the activation of the ATP-sensitive K/sup +/ current [I/sub K(ATP)/], the inhibition of the Na/sup +//K/sup +/ pump current (I/sub NaK/) and the appearance of an ischemic Na/sup +/ inward current (I/sub 0Na/) on [K/sup +/]/sub 0/ in the absence of coronary flow using computer modelling. Our results show that the simultaneous activation of these three mechanisms produces a fast increase of [K/sup +/]/sub 0/ during the first 11.6 min, which is mainly due to the enhancement of K/sup +/ efflux. Then, [K/sup +/]/sub 0/ stabilizes at a plateau level of 15.5 mmol/l. This biphasic time course is qualitatively and quantitatively similar to the increase of [K/sup +/]/sub 0/ observed experimentally.