Effects of Calcium on Structure and Function of the Human Red Blood Cell Membrane

  • Hermann Passow
  • Melanie Shields
  • Paul La Celle
  • Ryszard Grygorczyk
  • Wolfgang Schwarz
  • Reiner Peters

Abstract

The intracellular activity of ionized Ca++ in the red cell is below 0.4 nmoles/1 (Schatzmann, 1973; Simons, 1982; Lew et al., 1982b) and hence much lower than calculated from intracellular Ca++ content divided by red cell volume (Lichtman and Weed, 1973). This indicates that much of the Ca++ is bound to the cell membrane (Lichtman and Weed, 1973; La Celle et al., 1973; Porzig and Stoffel, 1978) and intracellular constituents. The latter include the phosphoric acid esters and hemoglobin (Ferreira and Lew, 1977), all of which act as Ca++ buffers. The low intracellular Ca++ activity is maintained although the membrane is leaky for Ca++ (Ferreira and Lew, 1977) and the concentration of free Ca++ in blood plasma (about 1200 nmoles/1) exceeds that in cytosol by about four orders of magnitude. The enormous gradient is balanced by a powerful Ca++ pump (for review see Schatzmann, 1983). At 37°C, the maximal rate of pumping is about 10 mmoles/1 cells/h. The half saturation concentration (K1/2) of the pump, and hence one of the essential factors that determines tne steady state Ca++ concentration, depends on the conditions inside the cell: the concentration of the energy supplying substrate ATP, the concentration of the activating calmodulin, and the concentration of Mg++ (calmodulin activates maximally when 1 Mg++ and 3 Ca++ ions are complexed). Under physiological conditions, K1/2 seems to be about 0.3 µmole/1 (Downes and Michel1, 1981).

Keywords

Permeability Citrate Anemia Lysine Trypsin 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Allan, D. and Thomas, P., 1981, The effects of Ca2+ and Sr2+ on Ca2+-sensitive biochemical changes in human erythrocytes and their membranes, Biochem. J., 198:441–44Google Scholar
  2. Anderson, D.R., Davis, J.L. and Carraway, K.L., 1977, Calcium-promoted changes of the human erythrocyte membrane, J. Biol. Chem., 252:6617–662.Google Scholar
  3. Brown, A.M. and Lew, V.L., 1983, The effect of intracellular calcium on the sodium pump of human red cells, J. Physiol, 343:455–493.Google Scholar
  4. Downes, P. and Michel 1, R.H., 1981, Human erythrocyte membranes exhibit a cooperative calmodulin-dependent Ca2+-ATPase of high calcium sensitivity, Nature, 290: 270–271.Google Scholar
  5. Downes, P. and Michel 1, R.H., 1981, Human erythrocyte membranes exhibit a cooperative calmodulin-dependent Ca2+-ATPase of high calcium sensitivity, Nature, 290:270–271.Google Scholar
  6. Eaton7~JTW., Skelton, T.D., Swofford, H.S., Kolpin, C.E. and Jacobs, H.S., 1973, Elevated erythrocyte calcium in sickle cell disease, Nature, 246: 105–106.Google Scholar
  7. Feig, S.A. and Bassilan, S., 1974, Abnormal RBC Ca2+ metabolism in hereditary spherocytosis (H.S.), Blood, 44: 937.Google Scholar
  8. Ferreira, H.G. and Lew, Y.L., 1977, Passive Ca transport and cytoplasmic buffering in intact red cells, ini: “Membrane Transport in Red Cells,” J.C. Ellory and V.L. Lew, eds., pp. 53–91, Academic Press, London.Google Scholar
  9. Foder, B. and Scharff, O., 1981, Decrease of apparent calmodulin affinity of erythrocyte (Ca2 + Mg2+)-ATPase at low Ca2+ concentrations, Biochem. Biophys. Acta, 649:367–37.Google Scholar
  10. Grygorczyk, R. and Schwarz, W., 1983, Properties of the Ca2+-activated K+ conductance of human red cells as revealed by the patch clamp technique, Cell Calcium, 4: 499–51.CrossRefGoogle Scholar
  11. Grygorczyk, R., Schwarz, W. and Passow, H., 1984, Ca2+-activated K+ channels in human red cells, Biophys. J., 45:693–69.Google Scholar
  12. Hamill, O.P., 1981, Potassium channel currents in human red blood cells, J. Physiol., 319:97P–98.Google Scholar
  13. Heinz, A. and Passow, H., 1980, Role of external potassium in the calcium-induced potassium efflux from human red blood cell ghosts, J. Memb. Biol., 57:119–13.Google Scholar
  14. HochmutFT7 R.M., 1982, Solid and liquid behaviour of red cell membrane, Ann. Rev. Biophys. Bioeng., 11:43–5.Google Scholar
  15. Hochmuth, R.M., Mohandas, N., Blackshear, Jr., P.L., 1973, Measurement of the elastic modulus for red cell membrane using a fluid mechanical technique, Biophys. J., 13:747–76.Google Scholar
  16. Hoffman, J.F., Yingst, D.R., Goldinger, R.M., Blum, R.M. and Knauf, P.A., 1980, On the mechanism of Ca-dependent K transport in human red blood cells, in: “Membrane Transport in Erythrocytes,” U.Y. Lassen, H.H. Ussing,T.O. Wieth, eds., pp. 178–19, Munksgaard, Copenhagen.Google Scholar
  17. King, Jr., L.E. and Morrison, M., 1977, Calcium effects on human erythrocyte membrane proteins, Biochem. Biophys. Acta, 471:162–17.Google Scholar
  18. Kirkpatrick, F.H., Hillman, D.G. and La Celle. P.L.. 1975, A23187 and red cells: Changes in deformabil ity, K+, Mg2+, Ca2+ and ATP, Experientia, 31: 653–65.Google Scholar
  19. La Celle, P.L., Kirkpatrick, F.H., Udkow, M.P. and Arkin, B., 1973, Membrane fragmentation and Ca++-membrane interaction: potential mechanisms of shape change in the senescent red cell, in: “Red Cell Shape,” M. Bessis, R.I. Weed, P.F. Leblond, eds., pp. 69–7, Springer-Verlag, New York.Google Scholar
  20. Lepke, S. and Passow, H., 1976, Effects of incorporated trypsin on anion exchange and membrane proteins in human red blood cell ghosts, Biochem. Biophys. Acta, 455:353–37.Google Scholar
  21. Lew, V.L., Bookchin, R.M., Brown, A.M. and Ferreira, H.G., 1980, Ca-sensitivity modulation, in: “Membrane Transport in Erythrocytes,” U.V. Lassen, H.H. Ussing, J.O. Wieth, eds., pp. 134–13, Munksgaard, Copenhagen.Google Scholar
  22. Lew, V.L., Muallem, S. and Seymour, C.A., 1982a, Properties of the Ca2+ activated K+ channel in one-step inside-out vesicles from human red cell membranes, Nature, 296: 742–74.Google Scholar
  23. Lew, Y.L., Tsien, R.Y. and Miner, C., 1982b, The physiological [Ca2+] level and pump-leak turnover in intact red cells measured with the use of an incorporated Ca++ chelator, Nature, 298: 478–48.Google Scholar
  24. Lichtman, M.A. and Weed, R.I., 1973, Divalent cation content of normal and ATP-depleted erythrocytes and erythrocyte membranes, in: “Red Cell Shape,” M. Bessis, R.I. Weed, P.F. Leblond, eds., pp. T9-9, Springer-Verlag, New York.Google Scholar
  25. Lorand, L., Bjerrum, O.J., Hawkins, M., Lowe-Krentz, L. and Siefring, Jr., G.E., 1983, Degradation of transmembrane proteins in Ca2+-enriched human erythrocytes, J. Biol. Chem., 258:5300–530.Google Scholar
  26. Lorand, L., Siefring, Jr., G.E. and Lowe-Krentz, L., 1978, Formation of γ-glutamyl-ɛ lysine bridges between membrane proteins by a Ca2+-regulated enzyme in intact erythrocytes, J. Supramol. Struc., 9:427–44.Google Scholar
  27. Palek, J., 1977, Red cell calcium content and transmembrane calcium movements in sickle cell anaemia, J. Lab. Clin. Med., 89:1365–137.Google Scholar
  28. Peters, R., 1983, Fluorescence microphotolysis, Naturwissenschaften, 70: 294–30.CrossRefGoogle Scholar
  29. Ponnappa, B.C., Greenquist, A.C. and Shohet, S.B., 1980, Calcium-induced changes in polyphosphoinositides and phosphatidate in normal erythrocytes, sickle cells and hereditary pyropoikilocytes, Biochem. Biophys. Acta, 598:494–50.Google Scholar
  30. Porzig, H., 19/b, Comparative study of the effects of propranolol and tetracaine on cation movements in resealed human red cell ghosts, J. Physiol, 249:27–4.Google Scholar
  31. Porzig, H., 1977, Studies on the cation permeability of human red cell ghosts, J. Memb. Biol., 31:317–34.Google Scholar
  32. Porzig, H. and Stoffel, D., 1978, Equilibrium binding of calcium fragmented human red cell membranes and its relation to calcium-mediated effects on cation permeability, J. Memb. Biol., 40:117–14.Google Scholar
  33. Schatzmann, H.J., 1973, Dependence on calcium concentration and stoichiometry of calcium pump in human red cells, J. Physiol, 235:551–56.Google Scholar
  34. Schatzmann, H.J., 1983, The red cell calcium pump, Ann. Rev. Physiol., 45:303–31.Google Scholar
  35. Schwarz, W. and Passow, H., 1983, Ca2+-activated K+ channels in erythrocytes and excitable cells, Ann. Rev. Physiol., 45:359–37.Google Scholar
  36. Shields, M., La Celle, P.L., Peters, R. and Passow, H., 1985, Modification of the red cell membrane by internal Ca+ + and trypsin: effects on mechanical properties and K+ channels, in preparation.Google Scholar
  37. Simons, T.J.B., 1976, The preparation of human red cell ghosts containing calcium buffers, J. Physiol, 256:209–22.Google Scholar
  38. Simons, T.J.B., 1982, A method for estimating free Ca within human red blood cells, with an application to the study of their Ca-dependent K permeability, J. Memb. Biol., 66:235–24.Google Scholar
  39. Steck, T.L., 1974, Organization of proteins in the human red blood cell membrane, J. Cell Biol., 62: 1–1.CrossRefGoogle Scholar
  40. Szasz, I., Sarkadi, B., Schubert, A. and Gardos, G., 1978, Effects of lanthanum on calcium-dependent phenomena in human red cells, Biochem. Biophys. Acta, 512:331–34.Google Scholar
  41. Weed, R.I., La Celle, P.L. and Merrill, E.W., 1969, Metabolic dependence of red cell deformability, J. Clin. Invest., 48:795–80.Google Scholar
  42. Wiley, J.S. and Gill, F.M., 19/b, Red cell calcium leak in congenital hemolytic anemia with extreme microcytosis, Blood, 47: 197–21.Google Scholar
  43. Yingst, D.R. and Hoffman, J.F., 1984, Ca-induced K transport in human red blood cell ghosts containing arsenazo III: Transmembrane interactions of Na, K and Ca and the relationship to the functioning Na-K pump, J. Gen. Physiol., 83:19–4.Google Scholar
  44. Yingst, D.R. and Marcovitz, M.J., 1983, Effect of haemolysate on calcium inhibition of the (Na-K+)-ATPase of human red blood cells, Biochem. Biophys. Res. Comm., 111:970–97.Google Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Hermann Passow
    • 1
  • Melanie Shields
    • 1
  • Paul La Celle
    • 2
  • Ryszard Grygorczyk
    • 1
  • Wolfgang Schwarz
    • 1
  • Reiner Peters
    • 1
  1. 1.Max-Planck-Institut fur BiophysikFrankfurt/MainFederal Republic of Germany
  2. 2.Department of Radiation Biology and BiophysicsUniversity of Rochester School of MedicineRochesterUSA

Personalised recommendations