Electrophysiologic and mechanical effects of metabolic inhibition of high-energy phosphate production in cultured chick embryo ventricular cells

Abstract

The early electrophysiological and mechanical effects of metabolic inhibition of high energy phosphate production were studied in cultured chick embryo heart cells. Selective inhibition of either glycolysis by 2-deoxyglucose in the presence of acetate or of oxidative phosphorylation by cyanide showed different effects. 2-deoxyglucose induced pronounced reduction in maximal diastolic potential and prolongation of excitation contraction delay, with only a moderate decrease of contractility and with only minimal changes in action potential duration. Cyanide, on the other hand, induced a profound negative inotropic effect and caused slowing of relaxation, shortening of action potential duration, a decrease in the upstroke of the action potential, and only a moderate decrease in the diastolic membrane potential. Exposure to 2-deoxyglucose and cyanide combined produced effects consistent with inhibition of both metabolic pathways. These observations are consistent with the hypothesis that these two metabolic pathways may have specific roles in fueling several energy-demanding functions of the myocardial cell.