Comparative effects of metabolic inhibition on the action potential from three experimental models of cardiac cells

Because of conflicting reports on the basic mechanisms responsible for the action potential changes produced by hypoxia or metabolic inhibitors, we investigated the effect of 2,4-dinitrophenol, substrate deprivation, and 2-deoxy-D-glucose on three preparations of rat myocardium: adult and newborn ventricle and cultured cells derived from neonatal rats. The latter exhibit slow action potentials in contrast to the other two, which show fast action potentials. Cultured cells were insensitive to 2,4-dinitrophenol and substrate deprivation but were markedly inhibited by blocking of glycolysis. The action potential of adult cells was shortened in the three conditions tested but was most sensitive to blocking of oxidative phosphorylation, which abolished propagated electrical activity after 15 min of exposure. The response of newborn ventricle was intermediate between the other two. Our data indicated that as far as maintenance of the membrane electrical properties is concerned, the relative importance of different metabolic pathways varies with development after birth or with time in culture.