Cell Volume Control and Ion Transport in a Mammalian Cell

  • E. K. Hoffmann
Part of the Proceedings in Life Sciences book series (LIFE SCIENCES)


There is general agreement that regulation of cellular volume reflects balance between passive and active ion movements across the cellular membrane with the colloid osmotic pressure of intracellular macrornolecules being offset by the extrusion of sodium ions from the cells. This pump-and-leak concept was developed about 25 years ago by Leaf (1959), Ussing (1960), and Tosteson and Hoffman (1960). In the course of time this concept still holds valid, but has proven to be somewhat simplistic. In recent years evidence has accumulated demonstrating that volume regulation in mammalian cells is achieved mainly via dynamic and controlled changes of the leak pathways (for references see Hoffmann 1978; Hoffmann et al. 1983; Hoffmann et al. 1984a) involving transient stimulation of normally dormant leak pathways (Hoffmann et al. 1984b). Furthermore, the “leaks” turns out to be a composite of a number of specific transport pathways involving also cotransport and exchange systems.


Regulatory Volume Decrease Ehrlich Ascites Tumor Cell Hypotonic Medium Volume Recovery Regulatory Volume Increase 
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  1. Aull F (1981) Potassium chloride cotransport in steady-state ascites tumor cells. Does bumetanide inhibit? Biochim Biophys Acta 643:339–345PubMedCrossRefGoogle Scholar
  2. Aull F (1982) Specific drug sensitive transport pathways for chloride and potassium ions in steady-state Ehrlich mouse ascites tumor cells. Biochim Biophys Acta 688:740–746PubMedCrossRefGoogle Scholar
  3. Cala PM (1977) Volume regulation by flounder red blood cells in anisotonic media. J Gen Physiol 69:537–552PubMedCrossRefGoogle Scholar
  4. Cala PM (1980) Volume regulation by Amphiuma red blood cells. The membrane potential and its implications regarding the nature of the ion-flux pathways. J Gen Physiol 76:683–708PubMedCrossRefGoogle Scholar
  5. Cala PM (1983) Volume regulation by red blood cells: Mechanisms of ion transport. Mol Psychol 4:33–52Google Scholar
  6. Ellory JC, Dunham PB (1980) Volume-dependent passive potassium transport in LK sheep red cells. In: Lassen UV, Ussing HH, Wieth JO (eds) Membrane transport in erythrocytes. Alfred Benzon Symposium XIV. Munksgaard, Copenhagen, pp 409–423Google Scholar
  7. Ellory JC, Dunham PB, Logue PJ, Stewart GW (1982) Anion-dependent cation transport in erythrocytes. Philos Trans R Soc London B Biol Sci 299:483–495PubMedCrossRefGoogle Scholar
  8. Fugelli K, Rohrs H (1980) The effect of Na+ and osmolarity on the influx and the steady state distribution of taurine and gamma-aminobutyric acid in flounder (Platichthys flesus) erythrocytes. Comp Biochem Physiol 67A:545–551CrossRefGoogle Scholar
  9. Geck P, Heinz E, Pietrzyk C, Pfeiffer B (1978) The effect of furosemide on the ouabain-insensitive K and Cl movement in Ehrlich cells. In: Straub RW, Bolis L (eds) Cell membrane receptors for drugs and hormones: a multidisciplinary approach. Raven, New York, pp 301–307Google Scholar
  10. Geck P, Pietrzyk C, Burckhardt B-C, Pfeiffer B, Heinz E (1980) Electrically silent co-transport of Na+, K+ and Cl- in Ehrlich cells. Biochim Biophys Acta 600:432–447PubMedCrossRefGoogle Scholar
  11. Grantham J, Lowe C, Dellasage M, Cole B (1977) Effect of hypotonic medium on K and Na content of proximal renal tubules. Am J Physiol 232:F42–49PubMedGoogle Scholar
  12. Grinstein S, Clarke CA, DuPre A, Rothstein A (1982a) Volume-induced increase of anion permeability in human lymphocytes. J Gen Physiol 80:801–823PubMedCrossRefGoogle Scholar
  13. Grinstein S, Clarke CA, Rothstein A (1982b) Increased anion permeability during volume regulation in human lymphocytes. Philos Trans R Soc London B Biol Sci 299:509–518PubMedCrossRefGoogle Scholar
  14. Grinstein S, DuPre A, Rothstein A (1982c) Volume regulation by human lymphocytes. Role of calcium. J Gen Physiol 79:849–868PubMedCrossRefGoogle Scholar
  15. Grinstein S, Clarke CA, Rothstein A (1983) Activation of Na+/H+ exchange in lymphocytes by osmotically-induced volume changes and by cytoplasmic acidification. J Gen Physiol 82:619–657PubMedCrossRefGoogle Scholar
  16. Hempling HG (1960) Permeability of the Ehrlich ascites tumor cell to water. J Gen Physiol 44:365–379PubMedCrossRefGoogle Scholar
  17. Hendil KB, Hoffmann EK (1974) Cell volume regulation in Ehrlich ascites tumor cells. J Cell Physiol 84:115–125PubMedCrossRefGoogle Scholar
  18. Hoffmann EK (1978) Regulation of cell volume by selective changes in the leak permeabilities of Ehrlich ascites tumor cells. In: Jørgensen CB, Skadhauge E (eds) Osmotic and volume regulation, Alfred Benzon Symposium XI. Munksgaard, Copenhagen, pp 397–417Google Scholar
  19. Hoffmann EK (1982) Anion exchange and anion-cation co-transport systems in mammalian cells. Phüos Trans R Soc London B Biol Sci 299:519–535CrossRefGoogle Scholar
  20. Hoffman EK (1983) Volume regulation by animal cells. In: Cossins AR, Shetterline PG (eds) Cellular acclimatization to environmental change Soc Exptl Biol Seminar Series 18. Cambridge University Press, Cambridge, pp 55–80Google Scholar
  21. Hoffmann EK (1985) Volume-dependent NaCl co-transport and volume-induced increase of K+ and Cl- permeability in Ehrlich cells. Fed Proc 44 (9):2513–2519PubMedGoogle Scholar
  22. Hoffmann EK, Lambert IH (1983) Amino acid transport and cell volume regulation in Ehrlich ascites tumour cells. J Physiol (Lond) 338:613–625Google Scholar
  23. Hoffmann EK, Simonsen LO, Sjøholm C (1979) Membrane potential chloride exchange, and chloride conductance in Ehrlich mouse ascites tumour cells. J Physiol 296:61–84PubMedGoogle Scholar
  24. Hoffmann EK, Sjøholm C, Simonsen LO (1983) Na+, Cl- cotransport in Ehrlich ascites tumor cells activated during volume regulation (regulatory volume increase). J Membr Biol 76:269–280PubMedCrossRefGoogle Scholar
  25. Hoffmann EK, Simonsen LO, Lambert IH (1984a) Volume-induced increase of K+ and Cl- permeability in Ehrlich ascites tumor cells. Role of internal Ca2+. J Membr Biol 78:211–222PubMedCrossRefGoogle Scholar
  26. Hoffmann EK, Lambert IH, Simonsen LO (1984b) Separate K+ and Cl- transport pathways activated by Ca2+ in Ehrlich mouse ascites tumour cells. J Physiol 357:62PGoogle Scholar
  27. Kregenow FM (1971) The response of duck erythrocytes to nonhemolytic hypotonic media. Evidence for a volume-controlling mechanism. J Gen Physiol 58:372–395PubMedCrossRefGoogle Scholar
  28. Kregenow FM (1974) Functional separation of the Na-K exchange pump from the volume controlling mechanism in enlarged duck red cells. J Gen Physiol 64:393–412PubMedCrossRefGoogle Scholar
  29. Kregenow FM (1981) Osmoregulatory salt transporting mechanisms: Control of cell volume in anisotonic media. Annu Rev Physiol 43:493–505PubMedCrossRefGoogle Scholar
  30. Lambert IH, Simonsen LO, Hoffmann EK (1984) Volume regulation in Ehrlich ascites tumour cells: pH sensitivity of the regulatory volume decrease, and role of the Ca2+-dependent K+ channel. Acta Physiol Scand 120:46AGoogle Scholar
  31. Lauf PK (1982) Evidence for chloride dependent potassium and water transport induced by hyposmotic stress in erythrocytes of the marine teleost. Opsanus tau. J Comp Physiol 146:9–16Google Scholar
  32. Leaf A (1959) Maintenance of concentration gradients and regulation of cell volume. Ann NY Acad Sci 72:396–404PubMedCrossRefGoogle Scholar
  33. McManus TJ, Schmidt III WF (1978) Ion and co-ion transport in avian red cells. In: Hoffman JF (ed) Membrane transport processes, vol 1. Raven, New York, pp 79–106Google Scholar
  34. Palfrey HC, Feit PW, Greengard P (1980) cAMP-stimulated cation cotransport in avian erythrocytes: inhibition by “loop” diuretics. Am J Physiol 238:C139–C148PubMedGoogle Scholar
  35. Parker JC (1983a) Hemolytic action of potassium salts on dog red blood cells. Am J Physiol 244: C313–C317PubMedGoogle Scholar
  36. Parker JC (1983b) Passive calcium movements in dog red blood cells: anion effects. Am J Physiol 244:C318–C323PubMedGoogle Scholar
  37. Parker JC (1983c) Volume-responsive sodium movements in dog red cells. Am J Physiol 244:C324–C330PubMedGoogle Scholar
  38. Roti-Roti LW, Rothstein A (1973) Adaptation of mouse leukemic cells (L5178Y) to anissotonic media I. Cell volume regulation. Exp Cell Res 79:295–310PubMedCrossRefGoogle Scholar
  39. Sarkadi B, Mack E, Rothstein A (1984) Ionic events during the volume response of human peripheral blood lymphocytes to hypotonic media. I. J Gen Physiol 83:497–512PubMedCrossRefGoogle Scholar
  40. Spring KR, Ericson AC (1982) Epithelial cell volume modulation and regulation. J Membr Biol 69: 167–176PubMedCrossRefGoogle Scholar
  41. Thornhill WB, Laris PC (1984) KCl loss and cell shrinkage in the Ehrlich ascites tumor cell induced by hypotonic media, 2-deoxyglucose and Propranolol. Biochem Biophys Acta 773:207–218PubMedCrossRefGoogle Scholar
  42. Tosteson DC, Hoffman JF (1960) Regulation of cell volume by activa cation transport in high and low potassium sheep red cells. J Gen Physiol 44:169–194PubMedCrossRefGoogle Scholar
  43. Ussing HH (1960) Active and passive transport of the alkali metal ions. In: Ussing HH, Kruhoffer P, Hess Thaysen J, Thorn NA (eds) The alkali metal ions in biology. Springer, Berlin Heidelberg New York, pp 45–143 (p 67)Google Scholar
  44. Ussing HH (1982) Volume regulation of frog skin epithelium. Acta Physiol Scand 114:363–369PubMedCrossRefGoogle Scholar
  45. Valdeolmillos M, Garcia-Sancho J, Herreros B (1982) Ca2+-dependent K+ transport in the Ehrlich ascites tumor cell. Biochim Biophys Acta 685:273–278PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1985

Authors and Affiliations

  • E. K. Hoffmann
    • 1
  1. 1.Institute of Biological Chemistry A, August Krogh InstituteUniversity of CopenhagenCopenhagen ØDenmark

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