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. 1974 Mar;53(3):745–755. doi: 10.1172/JCI107613

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

James S Wiley 1, Richard A Cooper 1
PMCID: PMC333055  PMID: 4812437

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 Mg2+, 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 Mg2+ 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.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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