Factors affecting the relative magnitudes of the sodium: potassium and sodium: sodium exchanges catalysed by the sodium pump

1. The effects of external potassium on sodium: potassium exchange and sodium: sodium exchange in human red cells have been estimated from measurements of ouabain-sensitive potassium influx and ouabain-sensitive sodium influx in media containing different concentrations of potassium.2. As the external potassium concentration is increased from zero to 5 mM, sodium:sodium exchange-as judged by ouabain-sensitive sodium influx-is progressively suppressed, and sodium:potassium exchange-as judged by ouabain-sensitive potassium influx-is progressively increased. Both exchanges are half-maximal between 1 and 2 mM-K, and at 5 mM-K sodium: sodium exchange becomes very small as sodium: potassium exchange approaches a maximum.3. Experiments have been carried out, mainly on resealed ghosts, to determine what factors affect the magnitude of the sodium:sodium exchange in potassium-free solutions.4. Sodium:sodium exchange does not occur in the absence of adenosine triphosphate (ATP).5. Ghosts containing high concentrations of sodium, no potassium and high concentrations of ATP show no ouabain-sensitive loss of sodium into potassium-free solutions. The ability to carry out sodium:sodium exchange can be restored by replacing most of the internal sodium with potassium or by preparing the cells so that they contain much more orthophosphate (P(i)) than ATP.6. Ghosts containing sodium in low concentration, potassium in high concentration and with a low [ATP]/([ADP].[P(i)]) ratio show a greater ouabain-sensitive loss of sodium into potassium-free media than into media containing potassium; i.e. external potassium reduces ouabain-sensitive sodium efflux.7. The effect of P(i) is not the result of competitive inhibition of the transport ATPase since P(i) at the concentrations used does not inhibit ATPase activity in fragmented ghosts.