Pinacidil-induced block of action potential propagation in ischaemic tissue: a simulation study

Abstract

During ischaemia, ATP-sensitive potassium current (I(K(ATP)))is activated in ventricular myocytes. The action potential (AP) duration becomes subsequently shorter in ischaemic zones, and inhomogeneities appear within the tissue, with possibility of propagation block and reentry. Pinacidil is a potassium channel opener, which has controversial effects. The aim of this study is to analize the mechanism of action by which this drug induces block of AP propagation. Simulations were carried out using a modified version of the Luo Rudy II model which included a formulation of (I(K(ATP))) and pinacidil effects. The simulated tissue included normal, border and central ischemic zones. From their results the authors hypothetize that AP propagation block occurs when calcium current is inactivated, due to pinacidil activation of I(K(ATP)) concomitant with sodium current depression.