Intracellular potassium. A determinant of the sodium-potassium pump rate

Normal human red cells which have had their intracellular sodium (Na(c)) reduced have a diminished Na-K pump rate, but only if intracellular potassium (K(c)) is high. If most of the K(c) is replaced by tetramethylammonium or choline, both ouabain-sensitive Na efflux and K influx are significantly increased even with Na(c) below normal. Cells with reduced Na(c) and high K(c) have an unchanged Na efflux if external potassium (K(ext)) is removed. In contrast, low-Na, low-K cells have a large ouabain-sensitive Na efflux which shows a normal response to removal of K(ext). Neither low-K nor high-K cells have an altered ouabain-sensitive K efflux. Measurement at constant low Na(c) and varying K(c) shows the pump Na efflux to be an inverse function of K(c). Thus, in low-Na cells, K(c) appears to act as an inhibitor of the pump. Inhibition by high K(c) can be seen even when Na(c) is normal. The effects attributed to K(c) are distinguished experimentally from other variables such as cell volume, adenosine triphosphate concentration, effects of the replacement cations, and the method used to alter intracellular cation concentrations. A role is proposed for K(c), in cooperation with Na(c), in regulating the pump rate of normal human red cells.