A Furosemide- Sensitive Cotransport of Sodium plus Potassium in the Human Red Cell

man red cell appear to be interrelated. This relationship was investigated under conditions in which either Na4 or K+ concentration outside the cell was varied or one cation was replaced by Mg2", choline+, or Li'. The effects of furosemide on Na+ and K+ movements were studied in the presence of ouabain. When ouabain was present, Na4 influx was higher with K4 ions externally than with other cations externally. Furosemide inhibited this K+-stimulated Na4 influx, but it had little effect when K+ was absent. Ouabain-insensi-tive K4 influx was stimulated two-fold by external Nae compared with other cations. Furosemide also inhibited this stimulation, but it had little effect when Mg`4 or choline4 replaced external Nae. Thus it was confirmed that synergism exists between the ouabain-insensitive in-fluxes of Na4 and K4 and it was demostrated that furo-semide inhibits this cooperative effect. The ouabain-insensitive influx of both K+ and Na4 showed a hyperbolic "saturating " dependence on the external concentration of the transported cation. Furosemide therefore elimi-nates a saturable component of influx of each cation. The net uptake of Na+ in the presence of ouabain was stimulated by K4 ions. A similar effect was observed with red cells, in which Li4 replaced nearly all the internal Nae plus K4 ions. In these cells, net Nae uptake was stimulated by external K+, and net K+ uptake was stim-ulated by external Na+. Furosemide inhibited this mutual stimulation of net cation entries. The inhibitory action of furosemide was not limited to inward flux and net movement of Na4 and K+. Furose