The Dependence on External Cation of Sodium and Potassium Fluxes Across the Human Red Cell Membrane at Low Temperatures

The fluxes of Na and K across the human red cell membrane have been studied as functions of temperature and external cation composition. In media containing any of a variety of organic compounds as the principal cation (choline, N-methyl-D-glucamine (NMDG), arginine, L-lysine and trimethyl-phenylammonium), the ouabain plus bumetanide-insensitive influxes and effluxes of Na and K displayed marked paradoxical temperature dependence such that the flux minimum, which normally occurs at about 8-10 degrees C in a NaCl medium, was shifted up to about 20 degrees C. Inhibitor and anion replacement studies excluded contributions by the major carrier-mediated systems evident at 37 degrees C. At 0 degrees C in NMDG, about 1 mM-external Na and 10 mM-external K were required half-maximally to inhibit the K and Na influxes respectively. When the K(86Rb) efflux in NMDG media at 0 degrees C was measured in the presence of low concentrations of a series of external inorganic ions and guanidine, the order of potency for reduction of the efflux was Li greater than Mg = Ca greater than Ba greater than Sr greater than Na greater than Rb = Cs = guanidine greater than K. The influxes of the neutral amino acid L-leucine and the cationic species L-lysine both showed simple monotonic temperature dependence in Na and NMDG media. These effects show that the permeability of the human red cell membrane to inorganic univalent cations at low temperatures is markedly dependent on the external ionic conditions. Low permeability is favoured by the presence of cations with a high charge density.