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

During acute myocardial ischemia, extra-cellular K⁺ accumulation has been proved to induce re-entrant arrhythmias. Despite the important of this phenomenon, the causes of cellular K⁺ loss remain still unknown. We investigated the simultaneous effect of the activation of the ATP-sensitive K⁺ current [I_K(ATP) ], the inhibition of the Na⁺/K⁺ pump current (I_NaK) and the appearance of an ischemic Na⁺ inward current (I_0Na) on [K⁺]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⁺]₀ during the first 11.6 min, which is mainly due to the enhancement of K⁺ efflux. Then, [K⁺ ]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⁺]₀ observed experimentally