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-o-sensitive or ouabain-sensitive current when most other membrane currents were inhibited, Control experiments showed that there were no K-o-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 by Na-i of 28 mM. Ouabain sensitivity was also measured, kind it was found that there wk re 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.