Skip to main content
SpringerLink
Log in
Book cover

Cell Volume and Signaling pp 77–88Cite as

Regulation of Na-K-2Cl Cotransport in Red Cells

  • Conference paper

Part of the book series: Advances in Experimental Medicine and Biology ((volume 559))

7. Conclusion

Different stimuli regulate phosphorylation of the cotransporter by activating or inhibiting distinct sets of cotransporter kinases and phosphatases, resulting in distinct patterns of phosphorylation. Phosphorylation of these sites may have a profound direct effect on transport rate, but this is not always the case. Phosphorylation may also determine how the transporter interacts with other regulatory proteins, perhaps helping the cell to integrate cotransporter activity in response to different, possibly conflicting, stimuli.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   149.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

9. References

  1. J. S. Wiley and R. A. Cooper, A furosemide-sensitive cotransport of sodium plus potassium in the human red cell, J. Clin. Invest. 53, 745–755 (1974).

    PubMed  CAS  Google Scholar 

  2. C. Lytle, in: Red Cell Membrane Transport in Health and Disease, edited by I. Bernhardt and J. C. Ellory (Springer, Berlin, 2003), 173–195.

    Google Scholar 

  3. J. M. Russell, Sodium-potassium-chloride cotransport, Physiol. Rev. 80, 211–276 (2000).

    PubMed  CAS  Google Scholar 

  4. M. Haas and B. Forbush, III, The Na-K-Cl cotransporter of secretory epithelia, Annu. Rev. Physiol. 62, 515–534 (2000).

    Article  PubMed  CAS  Google Scholar 

  5. M. Haas, The Na-K-Cl cotransporters, Am. J. Physiol. 267, C869–C885 (1994).

    PubMed  CAS  Google Scholar 

  6. M. Haas, Properties and diversity of (Na-K-Cl) cotransporters, Annu. Rev. Physiol. 51, 443–457 (1989).

    Article  PubMed  CAS  Google Scholar 

  7. E. Delpire and D. B. Mount, Human and murine phenotypes associated with defects in cation-chloride cotransport, Annu. Rev. Physiol. 64, 803–843 (2002).

    Article  PubMed  CAS  Google Scholar 

  8. P. Geck, C. Pietrzyk, B.-C. Burckhardt, B. Pfeiffer, and E. Heinz, Electrically silent cotransport of Na+, K+ and Cl− in Ehrlich cells, Biochim. Biophys. Acta 600, 432–447 (1980).

    Article  PubMed  CAS  Google Scholar 

  9. M. Haas, W. F. Schmidt, III, and T. J. McManus, Catecholamine-stimulated ion transport in duck red cells. Gradient effects in electrically neutral [Na+K+2Cl] co-transport, J. Gen. Physiol. 80, 125–147 (1982).

    Article  PubMed  CAS  Google Scholar 

  10. C. Lytle, T. J. McManus, and M. Haas, A model of Na-K-2Cl cotransport based on ordered ion binding and glide symmetry, Am. J. Physiol. 274, C299–C309 (1998).

    PubMed  CAS  Google Scholar 

  11. M. Haas and B. Forbush, III, [3H]Bumetanide binding to duck red cells, J. Biol. Chem. 261, 8434–8441 (1986).

    PubMed  CAS  Google Scholar 

  12. J. Duhm and B. O. Göbel, Role of the furosemide-sensitive Na+/K+ transport system in determining the steady-state Na+ and K+ content and volume of human erythrocytes in vitro and in vivo, J. Membr. Biol. 77, 243–254 (1984).

    Article  PubMed  CAS  Google Scholar 

  13. H. Mairbäurl, S. Schulz, and J. F. Hoffman, Cation transport and cell volume changes in maturing rat reticulocytes, Am. J. Physiol. 279, C1621–C1630 (2000).

    Google Scholar 

  14. N. Maassen, M. Foerster, and H. Mairbäurl, Red blood cells do not contribute to removal of K+ released from exhaustively working forearm muscle, J. Appl. Physiol. 85, 326–332 (1998).

    PubMed  CAS  Google Scholar 

  15. J. Duhm, Modes of furosemide-sensitive K (Rb) transport in human (and rat) erythrocytes: effects of Nao, Nai, Ki, pH, cell volume, and NEM., Fed. Proc. 46, 2383–2385 (1987).

    CAS  Google Scholar 

  16. T. Tepper, W. J. Sluiter, R. M. Huisman, and D. de Zeeuw, Erythrocyte Na+/Li+ countertransport and Na+/K+-2Cl− co-transport measurement in essential hypertension: useful diagnostic tools or failure? A meta-analysis of 17 years of literature, Clin. Sci. 95, 649–657 (1998).

    Article  PubMed  CAS  Google Scholar 

  17. C. Lytle and T. McManus, Coordinate modulation of Na-K-2Cl cotransport and K-Cl cotransport by cell volume and chloride, Am. J. Physiol. Cell. Physiol. 283, C1422–C1431 (2002).

    PubMed  CAS  Google Scholar 

  18. P. W. Flatman, Sodium and potassium transport in ferret red cells, J. Physiol. (Lond) 341, 545–557 (1983).

    CAS  Google Scholar 

  19. A. C. Hall and J. C. Ellory, Measurement and stoichiometry of bumetanide-sensitive (2Na:1K:3Cl) cotransport in ferret red cells, J. Membr. Biol. 85, 205–213 (1985).

    Article  PubMed  CAS  Google Scholar 

  20. P. W. Flatman and J. Creanor, Regulation of Na+-K+-2Cl− cotransport by protein phosphorylation in ferret erythrocytes, J. Physiol. (Lond) 517, 699–708 (1999).

    Article  CAS  Google Scholar 

  21. H. Mairbäurl and C. Herth, Na+-K+-2Cl− cotransport, Na+/H+ exchange, and cell volume in ferret erythrocytes, Am. J. Physiol. 271, C1603–C1611 (1996).

    PubMed  Google Scholar 

  22. P. W. Flatman and P. L. R. Andrews, Cation and ATP content of ferret red cells, Comp. Biochem. Physiol. 74A, 939–943 (1983).

    Article  CAS  Google Scholar 

  23. M. C. Muzyamba, A. R. Cossins, and J. S. Gibson, Regulation of Na+-K+-2Cl− cotransport in turkey red cells: the role of oxygen tension and protein phosphorylation, J. Physiol. (Lond) 517, 421–429 (1999).

    Article  CAS  Google Scholar 

  24. H. Mairbäurl and C. Lytle, Shrinkage and deoxygenation stimulate NKCC independent of Mgi in ferret red blood cells, FASEB J. 13, A716 (1999).

    Google Scholar 

  25. P. W. Flatman, Deoxygenation stimulates Na+-K+-2Cl− cotransport in ferret erythrocytes, J. Physiol. (Lond) 531, 122P–123P (2001).

    Google Scholar 

  26. G. Jiang, J. D. Klein, and W. C. O’Neill, Growth factors stimulate the Na-K-2Cl cotransporter NKCC1 through a novel Cl−-dependent mechanism, Am. J. Physiol. Cell. Physiol. 281, C1948–C1953 (2001).

    PubMed  CAS  Google Scholar 

  27. W. F. Schmidt, III and T. J. McManus, Ouabain-insensitive salt and water movements in duck red cells. II. Norepinephrine stimulation of sodium plus potassium cotransport, J. Gen. Physiol. 70, 81–97 (1977).

    Article  PubMed  CAS  Google Scholar 

  28. I. Giménez and B. Forbush, Short-term stimulation of the renal Na-K-Cl cotransporter (NKCC2) by vasopressin involves phosphorylation and membrane translocation of the protein, J. Biol. Chem. 278, 26946–26951 (2003).

    Article  PubMed  CAS  Google Scholar 

  29. M. E. O’Donnell, A. Martinez, and D. Sun, Endothelial Na-K-Cl cotransport regulation by tonicity and hormones: phosphorylation of cotransport protein, Am. J. Physiol. 269, C1513–C1523 (1995).

    PubMed  CAS  Google Scholar 

  30. M. Haas, D. McBrayer, and C. Lytle, [Cl−]i-dependent phosphorylation of the Na-K-Cl cotransport protein of dog tracheal epithelial cells, J. Biol. Chem. 270, 28955–28961 (1995).

    Article  PubMed  CAS  Google Scholar 

  31. C. Lytle and B. Forbush, III, Regulatory phosphorylation of the secretory Na-K-Cl cotransporter: modulation by cytoplasmic Cl, Am. J. Physiol. 270, C437–C448 (1996).

    PubMed  CAS  Google Scholar 

  32. C. M. Liedtke, R. Papay, and T. S. Cole, Modulation of Na-K-2Cl cotransport by intracellular Cl-and protein kinase C-δ in Calu-3 cells, Am. J. Physiol. Lung Cell. Mol. Physiol. 282, L1151–L1159 (2002).

    PubMed  CAS  Google Scholar 

  33. C. Lytle and B. Forbush, III, The Na-K-Cl cotransport protein of shark rectal gland. II. Regulation by direct phosphorylation, J. Biol. Chem. 267, 25438–25443 (1992).

    PubMed  CAS  Google Scholar 

  34. J. Torchia, C. Lytle, D. J. Pon, B. Forbush, III, and A. K. Sen, The Na-K-Cl cotransporter of avian salt gland. Phosphorylation in response to cAMP-dependent and calcium-dependent secretogogues, J. Biol. Chem. 267, 25444–25450 (1992).

    PubMed  CAS  Google Scholar 

  35. A. Tanimura, K. Kurihara, S. J. Reshkin, and R. J. Turner, Involvement of direct phosphorylation in the regulation of the rat parotid Na+-K+-2Cl− cotransporter, J. Biol. Chem. 270, 25252–25258 (1995).

    Article  PubMed  CAS  Google Scholar 

  36. P. W. Flatman, Regulation of Na-K-2Cl cotransport by phosphorylation and protein-protein interactions, Biochim. Biophys. Acta 1566, 140–151 (2002).

    Article  PubMed  CAS  Google Scholar 

  37. A. W. Flemmer, I. Giménez, B. F. X. Dowd, R. B. Darman, and B. Forbush, Activation of the Na-K-Cl cotransporter NKCC1 detected with a phospho-specific antibody, J. Biol. Chem. 277, 37551–37558 (2002).

    Article  PubMed  CAS  Google Scholar 

  38. J. D. Klein and W. C. O’Neill, Volume-sensitive myosin phosphorylation in vascular endothelial cells: correlation with Na-K-2Cl cotransport, Am. J. Physiol. 269, C1524–C1531 (1995).

    PubMed  CAS  Google Scholar 

  39. C. Lytle, Activation of the avian erythrocyte Na-K-Cl cotransport protein by cell shrinkage, cAMP, fluoride, and calyculin-A involves phosphorylation at common sites, J. Biol. Chem. 272, 15069–15077 (1997).

    Article  PubMed  CAS  Google Scholar 

  40. R. B. Darman and B. Forbush, A regulatory locus of phosphorylation in the N terminus of the Na-K-Cl cotransporter, NKCC1, J. Biol. Chem. 277, 37542–37550 (2002).

    Article  PubMed  CAS  Google Scholar 

  41. R. B. Darman, A. Flemmer, and B. Forbush, Modulation of ion transport by direct targeting of protein phosphatase type I to the Na-K-Cl cotransporter, J. Biol. Chem. 276, 34359–34362 (2001).

    Article  PubMed  CAS  Google Scholar 

  42. H. C. Palfrey and E. B. Pewitt, The ATP and Mg2+ dependence of Na+-K+-2Cl− cotransport reflects a requirement for protein phosphorylation: studies using calyculin A, Pflügers Arch. 425, 321–328 (1993).

    Article  PubMed  CAS  Google Scholar 

  43. J. D. Klein, S. T. Lamitina, and W. C. O’Neill, JNK is a volume-sensitive kinase that phosphorylates the Na-K-2Cl cotransporter in vitro, Am. J. Physiol. 277, C425–C431 (1999).

    PubMed  CAS  Google Scholar 

  44. K. Piechotta, J. Lu, and E. Delpire, Cation chloride cotransporters interact with the stress-related kinases Ste20-related proline-alanine-rich kinase (SPAK) and oxidative stress response 1 (OSR1), J. Biol. Chem. 277, 50812–50819 (2002).

    Article  PubMed  CAS  Google Scholar 

  45. B. F. X. Dowd and B. Forbush, PASK (proline-alanine-rich STE20-related kinase), a regulatory kinase of the Na-K-Cl cotransporter (NKCC1), J. Biol. Chem. 278, 27347–27353 (2003).

    Article  PubMed  CAS  Google Scholar 

  46. S. Fillon, S. Wärntges, J. Matskevitch et al., Serum-and glucocorticoid-dependent kinase, cell volume, and the regulation of epithelial transport, Comp. Biochem. Phys. A 130, 367–376 (2001).

    Article  CAS  Google Scholar 

  47. C. Lytle, A volume-sensitive protein kinase regulates the Na-K-2Cl cotransporter in duck red blood cells, Am. J. Physiol. 274, C1002–C1010 (1998).

    PubMed  CAS  Google Scholar 

  48. C. Di Ciano-Oliveira, G. Sirokmány, K. Szászi et al., Hyperosmotic stress activates Rho: differential involvement in Rho kinase-dependent MLC phosphorylation and NKCC activation, Am. J. Physiol. Cell. Physiol. 285, C555–C566 (2003).

    PubMed  Google Scholar 

  49. P. W. Flatman and V. L. Lew, Magnesium buffering in intact human red blood cells measured using the ionophore A23187, J. Physiol. (Lond) 305, 13–30 (1980).

    CAS  Google Scholar 

  50. P. W. Flatman, The effects of magnesium on potassium transport in ferret red cells, J. Physiol. (Lond) 397, 471–487 (1988).

    CAS  Google Scholar 

  51. I. Matskevich and P. W. Flatman, Regulation of Na+-K+-2Cl− cotransport by threonine phosphorylation in ferret red cells, J. Physiol. (Lond) 547.P, C20 (2003).

    Google Scholar 

  52. J. H. Hanke, J. P. Gardner, R. L. Dow et al., Discovery of a novel, potent, and Src family-selective tyrosine kinase inhibitor, J. Biol. Chem. 271, 695–701 (1996).

    Article  PubMed  CAS  Google Scholar 

  53. L. Tatton, G. M. Morley, R. Chopra, and A. Khwaja, The Src-selective kinase inhibitor PP1 also inhibits Kit and Bcr-Abl tyrosine kinases, J. Biol. Chem. 278, 4847–4853 (2003).

    Article  PubMed  CAS  Google Scholar 

  54. T. Akiyama and H. Ogawara, Use and specificity of genistein as inhibitor of protein-tyrosine kinases, Methods Enzymol. 201, 362–370 (1991).

    Article  PubMed  CAS  Google Scholar 

  55. T. Tamaoki, Use and specificity of staurosporine, UCN-01, and calphostin C as protein kinase inhibitors, Methods Enzymol. 201, 340–347 (1991).

    PubMed  CAS  Google Scholar 

  56. C. Lytle, J.-C. Xu, D. Biemesderfer, and B. Forbush, III, Distribution and diversity of Na-K-Cl cotransport proteins: a study with monoclonal antibodies, Am. J. Physiol. 269, C1496–C1505 (1995).

    PubMed  CAS  Google Scholar 

  57. I. Matskevich, D. K. Apps, and P. W. Flatman, The Na-K-2Cl cotransporter forms high molecular weight complexes in ferret red blood cell membranes, Pflügers Arch. 443,–S186 (2002).

    Google Scholar 

  58. M. L. Moore-Hoon and R. J. Turner, The structural unit of the secretory Na+-K+-2Cl− cotransporter (NKCC1) is a homodimer, Biochemistry 39, 3718–3724 (2000).

    Article  PubMed  CAS  Google Scholar 

  59. P. W. Flatman and J. Creanor, Stimulation of Na+-K+-2Cl− cotransport by arsenite in ferret erythrocytes, J. Physiol. (Lond) 519, 143–152 (1999).

    Article  CAS  Google Scholar 

  60. J. Randall, T. Thorne, and E. Delpire, Partial cloning and characterization of Slc12a2: the gene encoding the secretory Na+-K+-2Cl− cotransporter, Am. J. Physiol. 273, C1267–C1277 (1997).

    PubMed  CAS  Google Scholar 

  61. C. R. T. Vibat, M. J. Holland, J. J. Kang, L. K. Putney, and M. E. O’Donnell, Quantitation of Na+-K+-2Cl− cotransport splice variants in human tissues using kinetic polymerase chain reaction, Anal. Biochem. 298, 218–230 (2001).

    Article  PubMed  CAS  Google Scholar 

  62. T. Krarup, L. D. Jakobsen, B. S. Jensen, and E. K. Hoffmann, Na+-K+-2Cl− cotransport in Ehrlich cells: regulation by protein phosphatases and kinases, Am. J. Physiol. 275, C239–C250 (1998).

    PubMed  CAS  Google Scholar 

  63. S. Shenolikar and A. C. Nairn, Protein phosphatases: recent progress, Advances in Second Messenger and Phosphoprotein Research 23, 1–121 (1991).

    PubMed  CAS  Google Scholar 

  64. P. M. Bryan and L. R. Potter, The atrial natriuretic peptide receptor (NPR-A/GC-A) is dephosphorylated by distinct microcystin-sensitive and magnesium-dependent protein phosphatases, J. Biol. Chem. 277, 16041–16047 (2002).

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Membrane Biology Group, College of Medicine and Veterinary Medicine, The University of Edinburgh, Hugh Robson Building, George Square, Edinburgh, Scotland, EH8 9XD, UK

    Peter W Flatman

Authors
  1. Peter W Flatman
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Wright State University, Dayton, Ohio

    Peter K. Lauf  & Norma C. Adragna  & 

Rights and permissions

Reprints and permissions

Copyright information

© 2004 Springer Science+Business Media, Inc.

About this paper

Cite this paper

Flatman, P.W. (2004). Regulation of Na-K-2Cl Cotransport in Red Cells. In: Lauf, P.K., Adragna, N.C. (eds) Cell Volume and Signaling. Advances in Experimental Medicine and Biology, vol 559. Springer, Boston, MA . https://doi.org/10.1007/0-387-23752-6_7

Download citation

Publish with us

Policies and ethics

Search

Navigation