title: A furosemide-sensitive cotransport of sodium plus potassium in the human red cell.
abstract: The influxes of Na(+) and K(+) into the human red cell appear to be interrelated. This relationship was investigated under conditions in which either Na(+) or K(+) concentration outside the cell was varied or one cation was replaced by Mg(2+), choline(+), or Li(+). The effects of furosemide on Na(+) and K(+) movements were studied in the presence of ouabain. When ouabain was present, Na(+) influx was higher with K(+) ions externally than with other cations externally. Furosemide inhibited this K(+)-stimulated Na(+) influx, but it had little effect when K(+) was absent. Ouabain-insensitive K(+) influx was stimulated two-fold by external Na(+) compared with other cations. Furosemide also inhibited this stimulation, but it had little effect when Mg(2+) or choline(+) replaced external Na(+). Thus it was confirmed that synergism exists between the ouabain-insensitive influxes of Na(+) and K(+) and it was demostrated that furosemide inhibits this cooperative effect. The ouabain-insensitive influx of both K(+) and Na(+) showed a hyperbolic "saturating" dependence on the external concentration of the transported cation. Furosemide therefore eliminates a saturable component of influx of each cation. The net uptake of Na(+) in the presence of ouabain was stimulated by K(+) ions. A similar effect was observed with red cells, in which Li(+) replaced nearly all the internal Na(+) plus K(+) ions. In these cells, net Na(+) uptake was stimulated by external K(+), and net K(+) uptake was stimulated 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 Na(+) and K(+). Furosemide also inhibited the efflux of Na(+) into Na(+)-free media and the efflux of K(+) into K(+)-free media. It appeared, therefore, that the action of furosemide was not explained by inhibition of exchange diffusion. These data are consistent with an ouabain-insensitive transport process that facilitates the inward cotransport of Na(+) plus K(+)-ions, and that can produce a net movement of both ions. Although this process under some conditions mediates an equal bidirectional flux of both Na(+) and K(+), it cannot be defined as exchange diffusion. The contransport process is inhibited by furosemide.
mesh_terms: D001693:Biological Transport, Active / Q000187:drug effects; D002478:Cells, Cultured; D002794:Choline / Q000097:blood; D004058:Diffusion; D004357:Drug Synergism; D004912:Erythrocytes / Q000378:metabolism*; D005665:Furosemide / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008094:Lithium / Q000097:blood; D008274:Magnesium / Q000097:blood; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000097:blood*; D012964:Sodium / Q000097:blood*
chemical_list: D010042:Ouabain; D005665:Furosemide; D008094:Lithium; D012964:Sodium; D008274:Magnesium; D002794:Choline; D011188:Potassium