The coupling of downhill ion movements associated with reversal of the sodium pump in human red cells.

1. Previous work on the incorporation of inorganic phosphate (P(i)) into ATP has suggested reversal of the chemical reactions of the Na pump in human red cells. A study has now been made of the associated movements of Na and K.2. The efflux of K, and the influx and efflux of Na were measured. When the Ringer was without K, the loss of cell K was inhibited by ouabain, and the ouabain-sensitive component of K efflux (0.36 mu-equiv.ml.(-1).hr(-1)) required external Na.3. The exchange of Na was also inhibited by ouabain. When influx and efflux of Na were measured simultaneously in K-free Ringer there was an excess of ouabain-sensitive influx over efflux of about 0.36 mu-equiv.ml.(-1).hr(-1). This difference balanced the ouabain-sensitive K efflux, and was not found with 10 mM-external K. The Na and K movements appear to be coupled and to be mediated by reversal of the Na pump.4. The net uptake of Na sensitive to ouabain was 0.38 mu-equiv.ml.(-1).hr(-1) for red cells incubated in K-free Ringer, and the net loss of K under the same conditions was 0.58 mu-equiv.ml.(-1).hr(-1) in rough keeping with the unidirectional flux values.5. Oligomycin decreased Na influx and efflux to the same extent as ouabain.6. There appears to be a coupled downhill movement of Na and K that is abolished both by inhibitors of the Na pump and by external K which promotes normal transport of Na outwards and K inwards.