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1. The permeability of human red cells to ³⁶Cl^- and to [³⁵S]SO₄^2- was studied in the presence of various monovalent anions.

2. A maximum decrease of anion permeability was found in a study of the steady-state exchange of ³⁶Cl in a medium containing 120 mM salicylate. The exchange had a half-time of 3 hr at 0° C, a reduction of normal chloride permeability by a factor of 10⁵. The activation energy of chloride exchange decreased from a value of 45 to 22 kcal/mole in the interval between 0 and 10° C. Simultaneous determination of the permeability to potassium and chloride proved that salicylate induced a reversal of the normal selectivity of red cells at 0° C (permeability coefficient P_K of 3·5 x 10^-9 cm/sec to be compared with a P_Cl of 2 x 10^-9 cm/sec).

3. In contradistinction to the slow movement of ³⁶Cl, the exchange of [¹⁴C]salicylate was completed within 4 min, when red cells were suspended at 0° C in the salicylate medium.

4. A study of the sulphate permeability at 38° C showed that the rate of steady-state exchange decreased, when chloride was replaced by lyotropic anions other than bromide. The sequence of the permeability decrease was: Cl^- = Br^- < I^- < NO₃ < SCN^- < salicylate, the same sequence which previously has been shown to increase the permeability to sodium and potassium. The activation energies of sulphate exchange were 32 kcal/mole (chloride medium), and 38 kcal/mole (thiocyanate medium).

5. Sufficient data were obtained during the study to demonstrate that when equilibrium has been obtained, there is a good agreement between the values of ³⁶Cl (cell water)/³⁶Cl (extracellular water) and of {[³⁵S]SO₄ (cell water)/[³⁵S]SO₄ (extracellular water)}.

6. It is concluded that the anion-induced changes of permeability are due to binding of anions to fixed cationic charges in the red cell membrane.

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