Role of ATP-sensitive K+ channel current in ischemic arrhythmias.

In acute myocardial ischemia slow conduction and short refractoriness both predispose to cardiac arrhythmias. Moreover, spatial dispersion in these parameters, in part determined by inhomogeneity in extracellular potassium concentration ([K+]0), which develops within minutes, is considered highly arrhythmogenic. The incidence and time distribution of ventricular arrhythmias is determined by these electrophysiological changes and by factors pertinent to the experimental model. In the initial phase of ischemia, glibenclamide, a potent blocker of ATP-sensitive K+ channels (K+ATP channels), reduces the rate of increase in [K+]0 and therefore, presumably, also the inhomogeneity in [K+]0. During this phase of ischemia glibenclamide has an antiarrhythmic effect, which may be based on a reduction in inhomogeneity in [K+]0. In addition, glibenclamide prolongs the action potential of ischemic myocardium. Although under ischemic conditions action potential duration is no longer a reliable parameter or refractoriness, glibenclamide-induced prolongation or refractoriness may play a role in the prevention of arrhythmias. In contrast, openers of K+ATP channels increase the incidence of ventricular arrhythmias or, in other models, the time course of onset is accelerated. They shorten the duration of the action potential in ischemic tissue. In the globally ischemic rabbit heart, initial changes in [K+]0 are not influenced by cromakalim. It is concluded that activation of the K+ATP channel current during early myocardial ischemia potentially contributes to the development of ventricular arrhythmias. Particularly, the direct electrophysiological effect of increased K+ current is considered arrhythmogenic.