Computer model of the effects of pinacidil on ATP-sensitive potassium current

The activation of ATP-sensitive potassium current [I_K(ATP) ] during metabolic impairment or by addition of potassium channel openers (KCOs), such as pinacidil, shortens the action potential duration (APD). This effect supports the hypothesis that KCOs are proarrhythmical agents. However, controversies on this purpose make necessary to study the problem further. In this work, we have formulated a mathematical model of the effects of pinacidil on I_K(ATP) based on experimental data in order to simulate these effects on a cell or a tissue. We have introduced our formulation in the ventricular cardiac action potential model described by Luo and Rudy [1994] (phase II) completed with the formulation of I_K(ATP) by Ferrero et al. [1996]. The results of our theoretical model are in accordance with the estimated experimental values, that show the shortening of APD after the addition of pinacidil, specially in pathological situations. This work is a first step towards further simulations on myocardial tissue, which could help to elucidate the problem of arrhythmogenesis under the action of pinacidil