Principles of Cell Volume Regulation Ion Flux Pathways and the Roles of Anions

  • Peter M. Cala


The goal of this chapter is to discuss general principles of cell volume regulation (in response to osmotic swelling and shrinkage) with particular emphasis on the ion flux pathways. While other chapters in this volume deal with various aspects of neuronal, glial, or muscle cell function, the present chapter will draw upon data from studies performed on red blood cells. The emphasis upon blood cells reflects the relative ease with which volume regulation by cells in suspension can be studied and not the biological importance of volume regulation by such cells. While changes in the cell volume of circulating cells can result in changes in blood viscosity and altered rheologic properties, disruption of neural cell volume can result in altered cable properties and consequent effects upon neural integration.


Volume Regulation Loop Diuretic Ehrlich Ascites Tumor Cell Cell Volume Regulation Anion Conductance 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Adorante, J. S., and Cala, P. M., 1987, Activation of electroneutral K flux in Amphiuma red blood cells by N-ethylmaleimide: Distinction between K/H exchange and KCI cotransport, J. Gen. Physiol. 90: 209–227.PubMedCrossRefGoogle Scholar
  2. Altamirano, A. A., and Russell, J. M., 1987, Coupled Na/K/Cl efflux: “Reverse” unidirectional fluxes in squid giant axons, J. Gen. Physiol. 89: 669–686.PubMedCrossRefGoogle Scholar
  3. Bourne, P. K., and Cossins, A. R., 1984, Sodium and potassium transport in trout (Salmo gairdneri) erythrocytes, J. Physiol. (London) 347: 361–375.Google Scholar
  4. Cala, P. M., 1980, Volume regulation by Amphiuma blood cells. The membrane potential and its implication regarding the nature of the ion-flux pathways, J. Gen. Physiol. 76: 683–708.PubMedCrossRefGoogle Scholar
  5. Cala, P. M., 1983a, Volume regulation by red blood cells: Mechanism of ion transport, Mol. Physiol. 4: 33–52.Google Scholar
  6. Cala, P. M., 1983b, Cell volume regulation by Amphiuma blood cells. The role of Ca as a modulator of alkali/H exchange, J. Gen. Physiol. 82: 761–784.PubMedCrossRefGoogle Scholar
  7. Cala, P. M., 1985, Volume regulation by Amphiuma red blood cells: Strategies for identifying alkali metal/H transport, Fed. Prot.. 44: 2500–2507.Google Scholar
  8. Cala, P. M., Mandel, L. J., and Murphy, E., 1986, Measurement of cytosolic free Ca during volume regulation in Amphiuma red blood cells, Am. J. Physiol. 19: C423 - C429.Google Scholar
  9. Corcia, A., and Armstrong, W. M., 1983, KCI cotransport: A mechanism for basolateral chloride exit in Necturus gallbladder, J. Membr. Biol. 76: 173–182.PubMedCrossRefGoogle Scholar
  10. Duhm, J., 1987, Furosemide-sensitive K (Rb) transport in human erythrocytes: Modes of operation, dependence on extracellular and intracellular Na, kinetics, pH dependency, and the effect of cell volume and N-ethylmaleimide, J. Membr. Biol. 98: 15–32.PubMedCrossRefGoogle Scholar
  11. Duhm, J., and Gobel, B. O., 1984, Chloride-dependent, furosemide-sensitive K transport in human and rat erythrocytes. Dependence on external Na, internal Na, and cell volume, Pfluegers Arch. 402(Suppl.): RI 1Google Scholar
  12. Ellory, J. C., and Dunham, P. B., 1980, Volume-dependent passive potassium transport in LK sheep red cells, in: Membrane Transport in Erythrocytes ( U. V. Lassen, H. H. Ussing, and J. O. Wieth, eds.), Alfred Benzon Symposium XIV, Munksgaard, Copenhagen, pp. 409–423.Google Scholar
  13. Geck, P., and Heinz, E., 1986, The Na-K-2C1 cotransport system, J. Membr. Biol. 91: 97–105.PubMedCrossRefGoogle Scholar
  14. Geck, P., Pietrzyk, C., Burckhardt, B.-C., Pfeiffer, B., and Heinz, E., 1980, Electrically silent cotransport of Na+, K+, and Cl- in Ehrlich cells, Biochim. Biophys. Acta 600: 432–447.PubMedCrossRefGoogle Scholar
  15. Grinstein, S., and Rothstein, A., 1986, Topical review: Mechanisms and regulation of the Na/H exchanger, J. Membr. Biol. 90: 1–12.PubMedCrossRefGoogle Scholar
  16. Grinstein, S., Clark, C. A., DuPre, A., and Rothstein, A., 1982, Volume-induced increase of anion permeability in human lymphocytes, J. Gen. Physiol. 80: 801–823.PubMedCrossRefGoogle Scholar
  17. Grinstein, S., Rothstein, A., Sarkadi, B., and Gelfand, E. W., 1984, Responses of lymphocytes to anisotonic media: Volume-regulating behavior, Am. J. Physiol. 246: C204 - C215.PubMedGoogle Scholar
  18. Haas, M., and McManus, T. J., 1985, Effect of norepinephrine on swelling-induced potassium transport in duck red cells: Evidence against a volume-regulatory decrease under physiological conditions, J. Gen. Physiol. 85: 649–667.PubMedCrossRefGoogle Scholar
  19. Haas, M., Schmidt, W. F., and McManus, T. J., 1982, Catecholamine-stimulated ion transport in duck red cells. Gradient effects in electrically neutral [Na-K-2C1] co-transport, J. Gen. Physiol. 80: 125–147.PubMedCrossRefGoogle Scholar
  20. Hazama, A., and Okada, Y., 1987, Electrophysiological evidence for independent activation of K and CI conductances during regulatory volume decrease in cultured epithelial cells [abstract], Eur Soc. Comp. Physiol. Biochem. 9th Conference.Google Scholar
  21. Hoffmann, E. K., 1986, Anion transport systems in the plasma membrane of vertebrate cells, Biochim. Biophys. Acta. 864: 1–31.PubMedCrossRefGoogle Scholar
  22. Hoffmann, E. K., Simonsen, L. O., and Lambert, I. H., 1984, Volume-induced increase in K and Cl permeabilities in Ehrlich ascites tumor cells: Role for internal Ca, J. Membr. Biol. 78: 211–222.PubMedCrossRefGoogle Scholar
  23. Kaji, D., 1986, Volume-sensitive K transport in human erythrocytes, J. Gen. Physiol. 88: 719–738.PubMedCrossRefGoogle Scholar
  24. Knauf, P. A., 1979, Erythrocyte anion exchange and the band 3 protein. Transport kinetics and molecular structure, Curr. Top. Membr. Transp. 12: 249–363.CrossRefGoogle Scholar
  25. Kracke, G. R., Anatra, M. A., and Dunham, P. B., 1988, Asymmetry of Na-K-Cl cotransport in human erythrocytes, Am. J. Physiol. 254: C243 - C250.PubMedGoogle Scholar
  26. Kramhoft, B., Lambert, I. H., Hoffmann, E. K., and Jorgensen, F., 1986, Activation of C -dependent K transport in Ehrlich ascites tumor cells, Am. J. Physiol. 251: C369 - C379.PubMedGoogle Scholar
  27. Kregenow, F. M., 1971, The response of duck red cells to hypertonie media. Further evidence for a volume-controlling mechanism, J. Gen. Physiol. 58: 398–412.Google Scholar
  28. Lauf, P. K., 1982, Evidence for chloride-dependent potassium and water transport induced by hyposmotic stress in erythrocytes of the marine teleost, Opsanus tau, J. Comp. Physiol. 146: 9–16.Google Scholar
  29. Lauf, P. K., 1983, Thiol-dependent passive K/CI transport in sheep red cells: I. Dependence on chloride and external K [Rb] ions, J. Membr. Biol. 73: 237–246.PubMedCrossRefGoogle Scholar
  30. Livne, A., Grinstein, S., and Rothstein, A., 1987, Volume-regulating behavior of human platelets, J. Cell Physiol. 131: 354–363.PubMedCrossRefGoogle Scholar
  31. Lytle, C., and McManus, T. J., 1986, A minimal model of INa-K-2CI] co-transport with ordered binding and glide symmetry, J. Gen. Physiol. 88: 36a.Google Scholar
  32. Lytle, C., and McManus, T J., 1987, Effect of loop diuretics and stilbene derivatives on swelling-induced [K-CI] co-transport, J. Gen. Physiol. 90: 28a.Google Scholar
  33. McManus, T. J., Haas, M., Starke, L. C., and Lytle, C., 1985, The duck red cell model of volume-sensitive chloride-dependent cation transport, Ann. N.Y. Acad. Sci. 456: 183–186.PubMedCrossRefGoogle Scholar
  34. O’Grady, S. M., Palfrey, H. C., and Field, M., 1987, Characteristics and function of Na-K-Cl cotransport in epithelial tissues, Am. J. Physiol. 253: C177 - C192.PubMedGoogle Scholar
  35. Palfrey, H. C., Feit, P. W., and Greengard, P., 1980, cAMP-stimulated cation cotransport in avian erythrocytes: Inhibition by “loop” diuretics, Am. J. Physiol. 238: C139 - C148.Google Scholar
  36. Parker, J. C., 1983, Hemolytic action of potassium salts on dog red blood cells, Am. J. Physiol. 244: C313 - C317.PubMedGoogle Scholar
  37. Parker, J. C., 1984, Glutaraldehyde fixation of sodium transport in dog red blood cells, J. Gen. Physiol. 84: 789–803.PubMedCrossRefGoogle Scholar
  38. Parker, J. C., 1988, Na/H exchange and volume regulation in nonepithelial cells, in: Na/H Exchange ( S. Grinstein, ed.), CRC Press, Boca Raton, pp. 179–190.Google Scholar
  39. Parker, J. C., and Dunham, P. B., 1989, Passive cation transport, in: Red Cell Membranes: Structure, Function and Clinical Aspects ( P. Agre and J. Parker, eds.), Dekker, New York.Google Scholar
  40. Schmidt, W. F., III, and McManus, T. J., 1977, Ouabain-insensitive salt and water movements in duck red cells. I. Kinetics of cation transport under hypertonic conditions, J. Gen. Physiol. 70: 59–79.PubMedCrossRefGoogle Scholar
  41. Thornhill, W. B., and Laris, P. C., 1984, KCI loss and cell shrinkage in the Ehrlich ascites tumor cell induced by hypotonie media, 2-deoxyglucose, and propanolol, Biochim. Biophys. Acta 773: 207–218.PubMedCrossRefGoogle Scholar
  42. Tosteson, P. C., and Robertson, J. S., 1956, Potassium transport in duck red blood cells, J. Cell. Comp. Physiol. 47: 147–166.CrossRefGoogle Scholar
  43. Wieth, J. O., and Brahm, J., 1985, Cellular anion transport, in: The Kidney: Physiology and Pathophysiology ( D. W. Seldin and G. Giebisch, eds.), Raven Press, New York, pp. 49–89.Google Scholar

Copyright information

© Springer Science+Business Media New York 1990

Authors and Affiliations

  • Peter M. Cala
    • 1
  1. 1.Department of Human Physiology, School of MedicineUniversity of CaliforniaDavisUSA

Personalised recommendations