Effect of norepinephrine and heart rate on intracellular sodium activity and membrane potential in beating guinea pig ventricular muscle

Abstract

The effect of 3 μM norepinephrine (NE) on intracellular sodium activity (a(i)(Na)) and resting membrane potential was studied by continuous intracellular recordings with a conventional and an ion-selective microelectrode. The electrodes were impaled simultaneously in small (diameter, 0.3 mm) superfused trabeculae of the beating guinea pig ventricle at 37°C. In the absence of NE, changes of the beating rate produced an increase of a(i)(Na) by 1.5 ± 0.17 mM (from 0 to 1 Hz) and 1.9 ± 0.47 mM (from 0 to 2 Hz). In the presence of NE, there was a very small significant increase of a(i)(Na) during constant stimulation (1 Hz) and at [K+](o) of 4.7 and 11.5 mM. After 7 minutes of exposure, a(i)(Na) increased by 0.5 ± 0.19 mM (mean ± SEM, n = 4) at [K+](o) of 4.7 mM and by 0.5 ± 0.22 (n = 6) at [K+](o) of 11.5 mM. Resting membrane potential became more positive by 1 mV at both levels of [K+](o). The effect of NE became also clearly manifest from the configurational changes of action potentials (profound increase in plateau height and duration). Stimulation of the Na+-K+ pump by NE became manifest from the changes of resting membrane potential and a(i)(Na) after abrupt cessation of stimulation. The magnitude and the rate of the decrease in a(i)(Na) and the initial rate of hyperpolarization were significantly greater in the presence of NE than in its absence. Comparison of the effect of NE on the changes of a(i)(Na) during constant rate and after the transition from stimulation to quiescence suggests that the increase of Na+ influx after administration of NE is counterbalanced by an increased rate of Na+-K+ pumping in the beating guinea pig ventricle.