Effect of Norepinephrine and Heart Rate on Intracellular Sodium Activity and Membrane Potential in Beating Guinea Pig Ventricular Muscle

The effect of 3 μM norepinephrine (NE) on intracellular sodium activity (aⁱ_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 aⁱ_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 aⁱ_Na during constant stimulation (1 Hz) and at [K⁺]_o of 4.7 and 11.5 mM. After 7 minutes of exposure, aⁱ_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 aⁱ_Na after abrupt cessation of stimulation. The magnitude and the rate of the decrease in aⁱ_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 aⁱ_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.