The sensitivity of the sodium pump to external sodium.

1. When red cells are incubated in potassium-free solutions, ouabain-sensitive sodium efflux is nearly absent with 5 mM-Na externally, but increases as the external sodium concentration is reduced from 5 mM to zero. This increase suggests that the transport mechanism is very sensitive to small amounts of sodium at the outside surface of the cell membrane. Further evidence for such sensitivity has been obtained from the effects of external sodium on the relation between potassium influx and external potassium concentration.2. With 5 mM-[K](o), potassium influx is rather insensitive to [Na](o) but at low potassium concentrations even low levels of sodium inhibit.3. With 140 mM-[Na](o) the potassium influx curve is S-shaped below 1 mM [K](o). At much lower sodium concentrations, the S-shaped region and the value of [K](o) for which potassium influx is half-maximal are both shifted progressively towards zero. At 10 muM-[Na](o), potassium influx is half maximal at 0.14 mM-[K](o) and the curve is close to a rectangular hyperbola down to 22 muM-[K](o); there seems to be a trace of inflexion at about 15 muM-[K](o).4. When [Na](o) is reduced from 5 mM to zero, removal of the inhibitory effect of external sodium ions on sodium: potassium exchange could lead to an increase in sodium efflux into nominally potassium-free solutions if these solutions did in fact contain traces of potassium. Such traces could arise by leakage from the cells, but, in a number of experiments, direct measurements showed that [K](o) was too low to account in this way for all of the observed ouabain-sensitive sodium efflux. A further reason for rejecting this explanation is that ouabain-sensitive potassium loss into nominally (Na+K)-free solutions was unaffected by adding 5 mM-Na. (A slight increase in ouabain-resistant loss was observed.)5. The ouabain-sensitive efflux of sodium into (Na+K)-free solutions therefore seems to represent a mode of behaviour of the transport mechanism distinct both from the sodium: potassium exchange that occurs under physiological conditions and from the sodium: sodium exchange that occurs in K-free, Na-rich media.