Alteration of action potential during early ischemia in the heart

Abstract

Ischemic heart disease still is the most common cause of death in the world. Metabolic inhibition is typical for ischemic heart disease and heart failure and we investigated the effect of induced early ischemia and the changes of the action potential parameters in the isolated rabbit heart. In cardiac myocytes, L-type calcium current provides calcium for the activation of the contractile apparatus and is a crucial determinant of cardiac contractile activity. The suppression of L-type calcium current during ischemia is usually reported effect but our experiments revealed a dual respond of calcium current to the uncoupling of oxidative phosphorylation. When isoprenaline stimulated cardiac cells were exposed to FCCP, the uncoupler induced a biphasic effect on L-type calcium current. The exposure of the myocytes to FCCP evoked a rapid initial stimulation that was followed by a strong inhibition of L-type calcium current. We tested how this phenomenon is reflected in the action potential of isolated rabbit heart. Results showed that in the early phase of ischemia the action potential duration (APD) was briefly increased. At 20% repolarization APD increased up to 10% after 0.5 min of ischemia. This increase of APD was followed by a typical gradual decrease of APD when ischemia progresses. We attribute this dual change of APD to the biphasic changes of L-type calcium current and calcium transient increase in the early stage of ischemia in the heart