Na/K Pump Current in Guinea Pig Cardiac Myocytes and the Effect of Na Leak

Na/K Pump Current. Introduction : Steady‐State Na/K pump current (I p ) in adult guinea pig ventricular myocytes was studied to determine the effect on the Na/K pump of transmembrane Na leak, membrane potential, and pipette Na concentration. Methods and Results : Using conventional whole cell, patch clamp techniques, I p was identified as either K 0 ‐sensitive or ouabain‐sensitive current when most other membrane currents were inhibited. Control experiments showed that there were no K 0 ‐sensitive currents other than I p under the conditions of our experiments. I p was found to be similar to that reported by others being voltage dependent between −130 and 0 mV and having a half maximal activation hy Na i of 28 mM. Ouabain sensitivity was also measured, and it was found that there were two binding sites with the high affinity site comprising 5% to 10% of the total and having an apparent affinity 1000‐fold higher than the low affinity site. Apparent affinity of both sites was shifted about 10‐fold (higher affinity) by increasing Na i from 10 to 85 mM. When internally perfused with 0 Na solution, Na leak through the membrane was found to be linearly related to Na/K pump activity. In contrast to prior suggestions, I p was not correlated with series resistance when there was a large transmembrane Na gradient. Conclusion : These data suggest that, under conditions of high transmembrane Na gradient, Na leak through the membrane plays a significant role in determining Na/K pump activity.