The uncoupled extruson of Na+ through the Na+ pump

Abstract An ouabain-sensitive or cyanide-sensitive Na + efflux into media nominally free of Na + and K + has been reported in variety of animal cells. One possible explanation is that, under these peculiar circumstances, the Na + pump exchanges intracellular Na + for K + leaking out of the cells, the affinity for K + being highest in the absence of external Na + . In this paper we explored a number of alternative possibilities concerning the nature of this pump flux in human red cells. The results showed that: 1. 1. The ouabain-sensitive Na + efflux into Na + and K + -free media, is unaffected by the absence of internal K + ([K + ] i 2. 2. Intracellular ADP concentrations, low enough to inhibit the ouabain-sensitive Na + :Na + exchange, have no effect on the Na + efflux in the absence of Na + and K + provided is enough ATP to sustain a normal Na + :K + exchange. 3. 3. Starvation, which reduces the Na + :K + exchange proportionally more than the Na + :Na + exchange, in intact cells, also inhibits the ouabain-sensitive loss into media lacking both, Na + and K + . 4. 4. In the absence of external Na + , K + activates the ouabain-sensitive Na + efflux (probably saturated with internal Na + ) from low K + , hypotonically resealed ghosts, along a saturation-like curve with a K m of about 100 μM. 5. 5. Low concentrations of Na + in the medium inhibit the Na + loss through the pump in the absence and also in the presence of saturating concentrations of K + (10 mM). The effect of Na + is rather inconsistent and the reason for this variable behaviour remains unknown. It is suggested that this Na + efflux through the pump is uncoupled from the inward translocation of a cation and that it may be associated with a Na + -inhibitable spontaneous dephosphorylation of the Na + pump.