Na entry and Na‐K pump activity in murine, hamster, and human cells ‐ effect of monensin, serum, platelet extract, and viral transformation

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Abstract
The relationship between Na entry and the activity of the Na‐K pump has been investigated in a variety of cell types by testing the effect of the Naionophore monensin, mitogenic stimulation with serum and oncogenic transformation by SV40 and polyoma virus. We found that addition of monensin increases intracellular Na in quiescent cultures of murine, hamster, and human cells. In each case, the rise in intracellular Na by monensin is associated with an increase in the activity of the Na‐K pump, which was measured as ouabain‐inhibitable 86Rb uptake. The addition of serum to quiescent cultures stimulates 86Rb uptake in all cell types studied. Serum alone causes an increase in intracellular potassium with no consistent change in intracellular Na. In the presence of the Na‐K pump inhibitor ouabain, serum causes a marked increase in intracellular Na, with little change in intracellular K. This pattern is interpreted as indicating that the primary effect of serum is to increase Na entry into the cells. A low concentration of monensin (0.2 μg/ml) mimics the effect of serum on ion fluxes and content, which supports the conclusion that serum and monensin stimulate 86Rb uptake in the same manner, namely by increasing Na entry into the cells. In addition, a partially purified platelet extract stimulates Na entry and 86Rb uptake in quiescent 3T3 cells. Finally 3T3 cells transformed by SV40 or polyoma virus exhibit a higher rate of Na entry and of Na‐K pump activity than their untransformed 3T3 counterparts. All these results indicate that the rate of Na entry plays an important role in the regulation of the activity of the Na‐K pump and that an increase in Na and K movements is a rapid response elicited by serum in a variety of cell types.