Summary
The Ca++-mediated increase in K+-permeability of intact red blood cells (Gardos effect) was initiated by exposing cells to known concentrations of Ca++ (using EGTA buffers) in the presence of the ionophore A23187. The potency of quinine, an inhibitor of the response, was found to depend on the external K+ concentration. In K+-free solutions the concentration of quinine to achieve 50% inhibition (K 50) was 5 μm, but at 5mm K+ the required concentration was increased 20-fold to 100 μm. An increase in internal Na+ had the opposite effect, allowing a high potency of quinine despite the presence of external K+. Alterations in the internal K+ level, on the other hand, were without effect on theK 50, suggesting that the membrane potential is not a factor. This conclusion is supported by the lack of effect on quinine inhibition of substitution of Cl− by NO −3 , a considerably more permeant anion. The data are consistent with the hypothesis that quinine inhibits by competitively displacing K+ from an external binding site, the reported K+-activation site for the Ca++-mediated K+-permeability.
Similar content being viewed by others
References
Armando-Hardy, M., Ellory, J.C., Ferreira, H.G., Fleminger, S., Lew, V.L. 1975. Inhibition of the calcium-induced increase in the potassium permeability of human red blood cells by quinine.J. Physiol. (London) 250:32P
Blum, R.M., Hoffman, J.F. 1971. The membrane locus of Ca-stimulated K transport in energy depleted human red blood cells.J. Membrane Biol. 6:315
Blum, R.M., Hoffman, J.F. 1972. Ca-induced K transport in human red blood cells: Localization of the Ca-sensitive site to the inside of the membrane.Biochem. Biophys. Res. Commun. 46: 1146
Cass, A., Dalmark, M. 1973. Equilibrium dialysis of ions in nystatin-treated red cells.Nature New Biol. 244:47
Gardos, G. 1956. The permeability of the human erythrocytes to potassium.Acta Physiol. Acad. Sci. Hung. 10:185
Garrahan, P.J., Rega, A.F. 1967. Cation loading of red blood cells.J. Physiol. (London) 193:459
Goldman, D.E. 1943. Potential, impedance and rectification in membranes.J. Gen. Physiol. 27:37
Hoffman, J.F., Blum, R.M. 1977. On the nature of the transport pathway used for Ca-dependent K movement in human red blood cells.In: Membrane Toxicity. M.W. Miller and A.E. Shamoo, editors. pp. 381–405. Plenum Press, New York
Hunter, M.J. 1977. Human erythrocyte anion permeabilities measured under conditions of net charge transfer.J. Physiol. (London) 268:35
Knauf, P.A., Fuhrmann, G.F., Rothstein, S., Rothstein, A. 1977. The relationship between anion exchange and net anion flow across the human red blood cell membrane.J. Gen. Physiol. 69:363
Knauf, P.A., Riordan, J.R., Schuhmann, B., Wood-Guth, I., Passow, H. 1975. Calcium-potassium-stimulated net potassium efflux from human erythrocyte ghosts.J. Membrane Biol. 25:1
Kregenow, F., Hoffman, J.F. 1972. Some kinetic and metabolic characteristics of calcium-induced potassium transport in human red cells.J. Gen. Physiol. 60:406
Lew, V.L., Ferreira, H.G. 1976. Variable Ca-sensitivity of a K selective channel in intact red cell membranes.Nature (London) 263:336
Lew, V.L., Ferreira, H.G. 1978. Calcium transport and the properties of a calcium-activated potassium channel in red cell membranes.In: Current Topics in Membranes and Transport. F. Bronner and A. Kleinzeller, editors. Vol. 10. pp. 217–277. Academic Press, New York
Manninen, V. 1970. Movements of sodium and potassium ions and their tracers in propranolol-treated red cells and diaphragm muscle.Acta Physiol. Scand. Suppl. 355:1
Reed, P.W. 1976. Effects of the divalent cation ionophore A23187 on potassium permeability of rat erythrocytes.J. Biol. Chem. 251:3489
Reichstein, E. 1980. Effects of quinine on Ca++-induced K+ permeability of human red blood cells.Fed. Proc. 39:1714 (abstr.)
Riordan, J.R., Passow, H. 1971. Effects of calcium and lead on potassium permeability of human erythrocyte ghosts.Biochim. Biophys. Acta 249:601
Romero, P.J., Whittam, R. 1971. The control by internal calcium of membrane permeability to sodium and potassium.J. Physiol. (London) 214:481
Sachs, J.R. 1977. Kinetics of inhibition of the Na−K pump by external sodium.J. Physiol. (London) 264:449
Scharff, O. 1972. The influence of calcium ions on the preparation of the (Ca2++Mg2+)-activated membrane ATPase in human red cells.Scand. J. Clin. Lab. Invest. 30:313
Schwartzenbach, G., Flaschka, H. 1969. Complexometric Titrations. (2nd ed.) (Translation by H.M.N.H. Irving in collaboration with the authors.) Methuen, London
Simons, T.J.B. 1976a. Calcium-dependent potassium exchange in human red cell ghosts.J. Physiol. (London) 156:227
Simons, T.J.B. 1976b. Carbocyanine dyes inhibit Ca-dependent K efflux from human red cell ghosts.Nature (London) 264:467
Simons, T.J.B. 1979. Actions of a carbocyanine dye on calcium dependent potassium transport in human red cell ghosts.J. Physiol. (London) 228:481
Szasz, I., Sarkadi, B., Gardos, G. 1978. Effect of drugs on the calcium-dependent rapid potassium transport in calcium-loaded intact red cells.Acta Biochim. Biophys. Acad. Sci. Hung. 13:133
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Reichstein, E., Rothstein, A. Effects of quinine on Ca++-induced K+ efflux from human red blood cells. J. Membrain Biol. 59, 57–63 (1981). https://doi.org/10.1007/BF01870821
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF01870821