Skip to main content

Molecular Physiology of Mammalian K+-CL Cotransporters

  • Conference paper
Cell Volume and Signaling

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

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

Access this chapter

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

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

6. References

  1. S.C. Hebert, D.B. Mount and G. Gamba, Molecular physiology of cation-coupled Cl-cotransport: the SLC12 family, Pflugers Arch 447, 580–93 (2004).

    Article  PubMed  CAS  Google Scholar 

  2. P.B. Dunham, G.W. Stewart and J.C. Ellory, Chloride-activated passive potassium transport in human erythrocytes, Proc Natl Acad Sci U S A 77, 1711–5 (1980).

    Article  PubMed  CAS  Google Scholar 

  3. P.K. Lauf and B.E. Theg, A chloride dependent K+ flux induced by N-ethylmaleimide in genetically low K+ sheep and goat erythrocytes, Biochem Biophys Res Commun 92, 1422–8 (1980).

    Article  PubMed  CAS  Google Scholar 

  4. P.K. Lauf, and N.C. Adragna, K-Cl cotransport: properties and molecular mechanism, Cell Physiol Biochem 10, 341–54 (2000).

    Article  PubMed  CAS  Google Scholar 

  5. D.B. Mount and G. Gamba, Renal K-Cl cotransporters, Curr Opin Nephrol Hypertens 10, 685–692 (2001).

    Article  PubMed  CAS  Google Scholar 

  6. J.A. Payne, C. Rivera, J. Voipio and K. Kaila, Cation-chloride co-transporters in neuronal communication, development and trauma, Trends Neurosci 26, 199–206 (2003).

    Article  PubMed  CAS  Google Scholar 

  7. P.K. Lauf, J. Bauer, N.C. Adragna, H. Fujise, A.M. Zade-Oppen, K.H. Ryu and E. Delpire, Erythrocyte K-Cl cotransport: properties and regulation, Am J Physiol 263, C917–32 (1992).

    PubMed  CAS  Google Scholar 

  8. A.R. Cossins and J.S. Gibson, Volume-sensitive transport systems and volume homeostasis in vertebrate red blood cells, Journal of Experimental Biology 200, 343–52 (1997).

    PubMed  CAS  Google Scholar 

  9. A.C. Hall and J.C. Ellory, Evidence for the presence of volume-sensitive KCl transport in ‘young’ human red cells, Biochim Biophys Acta 858, 317–20 (1986).

    Article  PubMed  CAS  Google Scholar 

  10. C. Brugnara and D.C. Tosteson, Cell volume, K transport, and cell density in human erythrocytes, Am J Physiol 252, C269–76 (1987).

    PubMed  CAS  Google Scholar 

  11. C. Brugnara, H.F. Bunn and D.C. Tosteson, Regulation of erythrocyte cation and water content in sickle cell anemia, Science 232, 388–90 (1986).

    Article  PubMed  CAS  Google Scholar 

  12. C. Brugnara, Sickle cell disease: from membrane pathophysiology to novel therapies for prevention of erythrocyte dehydration, J Pediatr Hematol Oncol 25, 927–33 (2003).

    Article  PubMed  Google Scholar 

  13. P.K. Lauf, Kinetic comparison of ouabain-resistant K-Cl fluxes (K-Cl [Co]-transport) stimulated in sheep erythrocytes by membrane thiol oxidation and alkylation, Mol Cell Biochem 82, 97–106 (1988).

    PubMed  CAS  Google Scholar 

  14. P.K. Lauf, Volume and anion dependency of ouabain-resistant K-Rb fluxes in sheep red blood cells, Am J Physiol 255, C331–9 (1988).

    PubMed  CAS  Google Scholar 

  15. D. Kaji, Volume-sensitive K transport in human erythrocytes, J Gen Physiol 88, 719–38 (1986).

    Article  PubMed  CAS  Google Scholar 

  16. P. Geck, C. Pietrzyk, B.C. Burckhardt, B. Pfeiffer and E. Heinz, Electrically silent cotransport on Na+, K+ and Cl− in Ehrlich cells, Biochim Biophys Acta 600, 432–47 (1980).

    Article  PubMed  CAS  Google Scholar 

  17. R.H. Moseley, Downregulated in adenoma gene encodes a chloride transporter defective in congenital chloride diarrhea, Am J Physiol 276, G185–92 (1999).

    PubMed  CAS  Google Scholar 

  18. D.A. Scott, R. Wang, T.M. Kreman, V.C. Sheffield and L.P. Karniski, The Pendred syndrome gene encodes a chloride-iodide transport protein, Nat Genet 21, 440–3 (1999).

    Article  PubMed  CAS  Google Scholar 

  19. J.C. Ellory, A.C. Hall, S.O. Ody, H.C. Englert, D. Mania, and H.J. Lang, Selective inhibitors of KCl cotransport in human red cells, FEBS Lett 262, 215–8 (1990).

    Article  PubMed  CAS  Google Scholar 

  20. R.P. Garay, C. Nazaret, P.A. Hannaert and E.J. Cragoe, Jr., Demonstration of a [K+Cl]-cotransport system in human red cells by its sensitivity to [(dihydroindenyl)oxy]alkanoic acids: regulation of cell swelling and distinction from the bumetanide-sensitive [Na+K+Cl]-cotransport system, Mol Pharmacol 33, 696–701 (1988).

    PubMed  CAS  Google Scholar 

  21. D. Vitoux, O. Olivieri, R.P. Garay, E.J. Cragoe, Jr., F. Galacteros, and Y. Beuzard, Inhibition of K+ efflux and dehydration of sickle cells by [(dihydroindenyl)oxy]alkanoic acid: an inhibitor of the K+Cl cotransport system, Proc Natl Acad Sci U S A 86, 4273–6 (1989).

    Article  PubMed  CAS  Google Scholar 

  22. M. Saitta, S. Cavalier, R. Garay, E. Cragoe, Jr. and P. Hannaert, Evidence for a DIOA-sensitive [K+Cl]-cotransport system in cultured vascular smooth muscle cells, Am J Hypertens 3, 939–42 (1990).

    PubMed  CAS  Google Scholar 

  23. C.C. Armsby, C. Brugnara and S.L. Alper, Cation transport in mouse erythrocytes: role of K+-Cl cotransport in regulatory volume decrease, Am J Physiol 268, C894–902 (1995).

    PubMed  CAS  Google Scholar 

  24. S.M. Linton and M.J. O’Donnell, Contributions of K+-Cl cotransport and Na+/K+-ATPase to basolateral ion transport in Malpighian tubules of Drosophila melanogaster, J Exp Biol 202, 1561–1570 (1999).

    PubMed  CAS  Google Scholar 

  25. W. Su, B.E. Shmukler, M.N. Chernova, A.K. Stuart-Tilley, L. de Franceschi, C. Brugnara, and S.L. Alper, Mouse K-Cl cotransporter KCC1: cloning, mapping, pathological expression, and functional regulation, Am J Physiol 277, C899–C912 (1999).

    PubMed  CAS  Google Scholar 

  26. A. Mercado, L. Song, N. Vazquez, D.B. Mount and G. Gamba, Functional Comparison of the K+-Cl Cotransporters KCC1 and KCC4, J Biol Chem 275, 30326–30334 (2000).

    Article  PubMed  CAS  Google Scholar 

  27. E. Delpire and P.K. Lauf, Kinetics of DIDS inhibition of swelling-activated K-Cl cotransport in low K sheep erythrocytes, J Membr Biol 126, 89–96 (1992).

    PubMed  CAS  Google Scholar 

  28. N.C. Adragna and P.K. Lauf, Quinine and quinidine inhibit and reveal heterogeneity of K-Cl cotransport in low K sheep erythrocytes, J Membr Biol 142, 195–207 (1994).

    PubMed  CAS  Google Scholar 

  29. C.C. Armsby, A.K. Stuart-Tilley, S.L. Alper and C. Brugnara, Resistance to osmotic lysis in BXD-31 mouse erythrocytes: association with upregulated K-Cl cotransport, Am J Physiol 270, C866–77 (1996).

    PubMed  CAS  Google Scholar 

  30. D.M. Kaji and C. Gasson, Urea activation of K-Cl transport in human erythrocytes, Am J Physiol 268, C1018–25 (1995).

    PubMed  CAS  Google Scholar 

  31. P.K. Lauf, K+-Cl cotransport: ‘to be or not to be’ oxygen sensitive, J Physiol (Lond) 511, 1 (1998).

    Article  CAS  Google Scholar 

  32. I. Bize and P.B. Dunham, H2O2 activates red blood cell K-Cl cotransport via stimulation of a phosphatase. Am J Physiol 269, C849–55 (1995).

    PubMed  CAS  Google Scholar 

  33. A. Grzelak, J. Mazur and G. Bartosz, Peroxynitrite activates K+-Cl cotransport in human erythrocytes, Cell Biol Int 25, 1163–5 (2001).

    Article  PubMed  CAS  Google Scholar 

  34. P.K. Lauf and N.C. Adragna, Temperature-induced functional deocclusion of thiols inhibitory for sheep erythrocyte K-Cl cotransport, Am J Physiol 269, C1167–75 (1995).

    PubMed  CAS  Google Scholar 

  35. I. Bize, B. Guvenc, G. Buchbinder and C. Brugnara, Stimulation of human erythrocyte K-Cl cotransport and protein phosphatase type 2A by n-ethylmaleimide: role of intracellular Mg++, J Membr Biol 177, 159–68. (2000).

    Article  PubMed  CAS  Google Scholar 

  36. I. Bize, B. Guvenc, A. Robb, A., G. Buchbinder and C. Brugnara, Serine/threonine protein phosphatases and regulation of K-Cl cotransport in human erythrocytes, Am J Physiol 277, C926–36. (1999).

    PubMed  CAS  Google Scholar 

  37. I. Bize and P.B. Dunham, Staurosporine, a protein kinase inhibitor, activates K-Cl cotransport in LK sheep erythrocytes, Am J Physiol 266, C759–70 (1994).

    PubMed  CAS  Google Scholar 

  38. L. de Franceschi, L. Fumagalli, O. Olivieri, R. Corrocher, C.A. Lowell and G. Berton, Deficiency of Src family kinases Fgr and Hck results in activation of erythrocyte K/Cl cotransport, Journal of Clinical Investigation 99, 220–7 (1997).

    Article  PubMed  Google Scholar 

  39. A.R. Cossins, Y.R. Weaver, G. Lykkeboe and O.B. Nielsen, Role of protein phosphorylation in control of K flux pathways of trout red blood cells, Am J Physiol 267, C1641–50 (1994).

    PubMed  CAS  Google Scholar 

  40. P.W. Flatman, N.C. Adragna and P.K. Lauf, Role of protein kinases in regulating sheep erythrocyte K-Cl cotransport, Am J Physiol 271, C255–C263 (1996).

    PubMed  CAS  Google Scholar 

  41. J.R. Sachs, Soluble polycations and cationic amphiphiles inhibit volume-sensitive K-Cl cotransport in human red cell ghosts, Am J Physiol 266, C997–1005 (1994).

    PubMed  CAS  Google Scholar 

  42. V. Stein, I. Hermans-Borgmeyer, T.J. Jentsch and C.A. Hubner, Expression of the KCl cotransporter KCC2 parallels neuronal maturation and the emergence of low intracellular chloride, J Comp Neurol 468, 57–64 (2004).

    Article  PubMed  CAS  Google Scholar 

  43. W. Kelsch, S. Hormuzdi, E. Straube, A. Lewen, H. Monyer and U. Misgeld, Insulin-like growth factor 1 and a cytosolic tyrosine kinase activate chloride outward transport during maturation of hippocampal neurons, J Neurosci 21, 8339–47 (2001).

    PubMed  CAS  Google Scholar 

  44. C. Lytle, A volume-sensitive protein kinase regulates the Na-K-2Cl cotransporter in duck red blood cells, Am J Physiol 274, C1002–10. (1998).

    PubMed  CAS  Google Scholar 

  45. C.M. Gillen, S. Brill, J.A. Payne and B. Forbush, III, Molecular cloning and functional expression of the K-Cl cotransporter from rabbit, rat, and human. A new member of the cation-chloride cotransporter family, J Biol Chem 271, 16237–44 (1996).

    Article  PubMed  CAS  Google Scholar 

  46. J.A. Payne, T.J. Stevenson and L.F. Donaldson, Molecular characterization of a putative K-Cl cotransporter in rat brain. A neuronal-specific isoform, J Biol Chem 271, 16245–52 (1996).

    Article  PubMed  CAS  Google Scholar 

  47. K. Hiki, R.J. D’Andrea, J. Furze, J. Crawford, E. Woollatt, G.R. Sutherland, M.A. Vadas and J.R. Gamble, Cloning, characterization, and chromosomal location of a novel human K+-Cl− cotransporter, J Biol Chem 274, 10661–7 (1999).

    Article  PubMed  CAS  Google Scholar 

  48. D.B. Mount, A. Mercado, L. Song, J. Xu, A.L. George, Jr., E. Delpire, and G. Gamba, Cloning and characterization of KCC3 and KCC4, new members of the cation-chloride cotransporter gene family, J Biol Chem 274, 16355–16362 (1999).

    Article  PubMed  CAS  Google Scholar 

  49. C.A Hubner, V. Stein, I. Hermans-Borgmeyer, T. Meyer, K. Ballanyi and T.J. Jentsch, Disruption of KCC2 reveals an essential role of K-Cl cotransport already in early synaptic inhibition, Neuron 30, 515–24. (2001).

    Article  PubMed  CAS  Google Scholar 

  50. T. Boettger, C. Hubner, H. Maier, M. Rust, F. Beck and T. Jentsch, Deafness and renal tubular acidosis in mice lacking the K-Cl cotransporter KCC4, Nature 416, 874–878 (2002).

    Article  PubMed  CAS  Google Scholar 

  51. H.C. Howard, D.B. Mount, D. Rochefort, N. Byun, N. Dupre, J. Lu, X. Fan, L. Song, J.B. Riviere, C. Prevost, J. Horst, A. Simonati, B. Lemcke, R. Welch, R. England, F.Q. Zhan, A. Mercado, W.B. Siesser A.L. George, M.P. McDonald, J.P. Bouchard, J. Mathieu, E. Delpire and G.A. Rouleau, The K-Cl cotransporter KCC3 is mutant in a severe peripheral neuropathy associated with agenesis of the corpus callosum, Nat Genet 32, 384–392 (2002).

    Article  PubMed  CAS  Google Scholar 

  52. T. Boettger, M.B. Rust, H. Maier, T. Seidenbecher, M. Schweizer, D.J. Keating, J. Faulhaber, H. Ehmke, C. Pfeffer, O. Scheel, B. Lemcke, J. Horst, R. Leuwer, H.C. Pape, H. Volkl, C.A. Hubner and T.J. Jentsch, Loss of K-Cl co-transporter KCC3 causes deafness, neurodegeneration and reduced seizure threshold, Embo J 22, 5422–34 (2003).

    Article  PubMed  CAS  Google Scholar 

  53. E.J. Holtzman, S. Kumar, C.A. Faaland, F. Warner, P.J. Logue, S.J. Erickson, G. Ricken, J. Waldman and P.B. Dunham, Cloning, characterization, and gene organization of K-Cl cotransporter from pig and human kidney and C. elegans, Am J Physiol 275, F550–64 (1998).

    PubMed  CAS  Google Scholar 

  54. H. Ochiai, K. Higa and H. Fujise, Molecular identification of K-CL cotransporter in dog erythroid progenitor cells, J Biochem (Tokyo) 135, 365–74 (2004).

    CAS  Google Scholar 

  55. F. Larsen, J. Solheim, T. Kristensen, A.B. Kolsto and H. Prydz, A tight cluster of five unrelated human genes on chromosome 16q22.1, Hum Mol Genet 2, 1589–95 (1993).

    PubMed  CAS  Google Scholar 

  56. G.P. Zhou, C. Wong, R. Su, S.C. Crable, K.P. Anderson and P.G. Gallagher, Human potassium chloride cotransporter 1 (SLC12A4) promoter is regulated by AP-2 and contains a functional downstream promoter element, Blood 103, 4302–9 (2004).

    Article  PubMed  CAS  Google Scholar 

  57. G.H. Clayton, G.C. Owens, J.S. Wolff and R.L. Smith, Ontogeny of cation-Cl− cotransporter expression in rat neocortex, Brain Res Dev Brain Res 109, 281–92 (1998).

    Article  PubMed  CAS  Google Scholar 

  58. C. Kanaka, K. Ohno, A. Okabe, K. Kuriyama, T. Itoh, A. Fukuda and K. Sato, The differential expression patterns of messenger RNAs encoding K-Cl cotransporters (KCC1,2) and Na-K-2Cl cotransporter (NKCC1) in the rat nervous system. Neuroscience 104, 933–46 (2001).

    Article  PubMed  CAS  Google Scholar 

  59. D.H. Ellison, H. Velazquez and F.S. Wright, Stimulation of distal potassium secretion by low lumen chloride in the presence of barium, Am J Physiol 248, F638–49 (1985).

    PubMed  CAS  Google Scholar 

  60. D.H. Ellison, H. Velazquez and F.S. Wright, Unidirectional potassium fluxes in renal distal tubule: effects of chloride and barium, Am J Physiol 250, F885–94 (1986).

    PubMed  CAS  Google Scholar 

  61. J.B. Amorim, M.A. Bailey, R. Musa-Aziz, G. Giebisch and G. Malnic, Role of luminal anion and pH in distal tubule potassium secretion, Am J Physiol Renal Physiol 284, F381–8 (2003).

    PubMed  CAS  Google Scholar 

  62. C.M. Gillen and B. Forbush, III, Functional interaction of the K-Cl cotransporter (KCC1) with the Na-K-Cl cotransporter in HEK-293 cells, Am J Physiol 276, C328–36. (1999).

    PubMed  CAS  Google Scholar 

  63. M. Haas and B. Forbush, III, The Na-K-Cl cotransporter of secretory epithelia. Annu Rev Physiol 62, 515–34 (2000).

    Article  PubMed  CAS  Google Scholar 

  64. C. Plata, P. Meade, N. Vazquez, S.C. Hebert and G. Gamba, Functional properties of the apical Na+-K+-2Cl-cotransporter isoforms, J Biol Chem 277, 11004–12 (2002).

    Article  PubMed  CAS  Google Scholar 

  65. P. Isenring, S.C. Jacoby, J. Chang and B. Forbush, Mutagenic mapping of the Na-K-Cl cotransporter for domains involved in ion transport and bumetanide binding, J Gen Physiol 112, 549–58 (1998).

    Article  PubMed  CAS  Google Scholar 

  66. A. Mercado, D.B. A., Mount, N. Vazquez, L. Song and G. Gamba, Functional characteristics of the renal KCCs, Faseb J 14, A341 (2000).

    Google Scholar 

  67. J.A. Payne, Functional characterization of the neuronal-specific K-Cl cotransporter: implications for [K+]o regulation, Am J Physiol 273, C1516–C1525 (1997).

    PubMed  CAS  Google Scholar 

  68. L. Song, et.al., Molecular, functional, and genomic characterization of human KCC2, the neuronal K-Cl cotransporter, Molecular Brain Research 103, 91–105 (2002).

    Article  PubMed  CAS  Google Scholar 

  69. P.K. Lauf, J. Zhang, E. Delpire, R.E.W. Fyffe, D.B. Mount and N.C. Adragna, Erythrocyte K-Cl cotransport: immunocytochemical and functional evidence for more than one KCC isoform in HK and LK sheep red blood cells, Comp Biochem Physiol 130, 499–509 (2002).

    Google Scholar 

  70. N. Vardi, L.L. Zhang, J.A. Payne and P. Sterling, Evidence that different cation chloride cotransporters in retinal neurons allow opposite responses to GABA. J Neurosci 20, 7657–63 (2000).

    PubMed  CAS  Google Scholar 

  71. T.Q. Vu, J.A. Payne and D.R. Copenhagen, Localization and developmental expression patterns of the neuronal K-Cl cotransporter (KCC2) in the rat retina, J Neurosci 20, 1414–23 (2000).

    PubMed  CAS  Google Scholar 

  72. R. Miles, Neurobiology. A homeostatic switch, Nature 397, 215–6 (1999).

    Article  PubMed  CAS  Google Scholar 

  73. J. Yamada, A. Okabe, H. Toyoda, W. Kilb, H.J. Luhmann and A. Fukuda, Cl-uptake promoting depolarizing GABA actions in immature rat neocortical neurones is mediated by NKCC1, J Physiol 557, 829–41 (2004).

    Article  PubMed  CAS  Google Scholar 

  74. A. Fukuda, K. Muramatsu, A. Okabe, Y. Shimano, H. Hida, I. Fujimoto and H. Nishino, Changes in intracellular Ca2+ induced by GABAA receptor activation and reduction in Cl gradient in neonatal rat neocortex, J Neurophysiol 79, 439–46. (1998).

    PubMed  CAS  Google Scholar 

  75. X. Leinekugel, I. Medina, I. Khalilov, Y. Ben-Ari and R. Khazipov, Ca2+ oscillations mediated by the synergistic excitatory actions of GABA(A) and NMDA receptors in the neonatal hippocampus, Neuron 18, 243–55. (1997).

    Article  PubMed  CAS  Google Scholar 

  76. S. Marty, B. Berninger, P. Carroll and H. Thoenen, GABAergic stimulation regulates the phenotype of hippocampal interneurons through the regulation of brain-derived neurotrophic factor, Neuron 16, 565–70. (1996).

    Article  PubMed  CAS  Google Scholar 

  77. K. Ganguly, A.F. Schinder, S.T. Wong and M. Poo, Gaba itself promotes the developmental switch of neuronal gabaergic responses from excitation to inhibition, Cell 105, 521–32. (2001).

    Article  PubMed  CAS  Google Scholar 

  78. J. Kirsch and H. Betz, Glycine-receptor activation is required for receptor clustering in spinal neurons, Nature 392, 717–20. (1998).

    Article  PubMed  CAS  Google Scholar 

  79. C. Rivera, J. Voipio, J.A. Payne, E. Ruusuvuori, H. Lahtinen, K. Lamsa, U. Pirvola, M. Saarma and L. Kaila, The K+-Cl cotransporter KCC2 renders GABA hyperpolarizing during neuronal maturation, Nature 397, 251–255 (1999).

    Article  PubMed  CAS  Google Scholar 

  80. J. Lu, M. Karadsheh and E. Delpire, Developmental regulation of the neuronal-specific isoform of the KCl cotransporter, KCC2, in postnatal rat brains, J Neurobiology 39, 558–568 (1999).

    Article  CAS  Google Scholar 

  81. W. Jarolimek, A. Lewen and U. Misgeld, A furosemide-sensitive K+-Cl cotransporter counteracts intracellular Cl accumulation and depletion in cultured rat midbrain neurons, J Neurosci 19, 4695–704 (1999).

    PubMed  CAS  Google Scholar 

  82. Y. Kakazu, S. Uchida, T. Nakagawa, N. Akaikeand and J. Nabekura, Reversibility and cation selectivity of the K+-Cl cotransport in rat central neurons, J Neurophysiol 84, 281–8. (2000).

    PubMed  CAS  Google Scholar 

  83. R.A. DeFazio, S. Keros, S., M.W. Quick and J.J. Hablitz, Potassium-coupled chloride cotransport controls intracellular chloride in rat neocortical pyramidal neurons, J Neurosci 20, 8069–76 (2000).

    PubMed  CAS  Google Scholar 

  84. K. Haug, M. Warnstedt, A.K. Alekov, T. Sander, A. Ramirez, B. Poser, S. Maljevic, S. Hebeisen, C. Kubisch, J. Rebstock, S. Horvath, K. Hallmann, J.S. Dullinger, B. Rau, F. Haverkamp, S. Beyenburg, H. Schulz, D. Janz, B. Giese, G. Muller-Newen, P. Propping, C.E. Elger, C. Fahlke, H. Lerche and A. Heils, Mutations in CLCN2 encoding a voltage-gated chloride channel are associated with idiopathic generalized epilepsies, Nat Genet 33, 527–32 (2003).

    Article  PubMed  CAS  Google Scholar 

  85. J.R. Williams, J.W. Sharp, V.G. Kumari, M. Wilson and J.A. Payne, The neuron-specific K-Cl cotransporter, KCC2. Antibody development and initial characterization of the protein, J Biol Chem 274, 12656–12664 (1999).

    Article  PubMed  CAS  Google Scholar 

  86. A.I. Gulyas, A. Sik, J.A. Payne, K. Kaila and T.F. Freund, The KCl cotransporter, KCC2, is highly expressed in the vicinity of excitatory synapses in the rat hippocampus, Eur J Neurosci 13, 2205–17. (2001).

    Article  PubMed  CAS  Google Scholar 

  87. H. Li, J. Tornberg, K. Kaila, M.S. Airaksinen and C. Rivera, Patterns of cation-chloride cotransporter expression during embryonic rodent CNS development, Eur J Neurosci 16, 2358–70 (2002).

    Article  PubMed  Google Scholar 

  88. S. Mikawa, C. Wang, F. Shu, T. Wang, A. Fukuda and K. Sato, Developmental changes in KCC1, KCC2 and NKCC1 mRNAs in the rat cerebellum, Brain Res Dev Brain Res 136, 93–100 (2002).

    Article  PubMed  CAS  Google Scholar 

  89. A. Ludwig, H. Li, M. Saarma, K. Kaila and C. Rivera, Developmental up-regulation of KCC2 in the absence of GABAergic and glutamatergic transmission, Eur J Neurosci 18, 3199–206 (2003).

    Article  PubMed  Google Scholar 

  90. S. Titz, M. Hans, W. Kelsch, A. Lewen, D. Swandulla and U. Misgeld, Hyperpolarizing inhibition develops without trophic support by GABA in cultured rat midbrain neurons, J Physiol 550, 719–30 (2003).

    Article  PubMed  CAS  Google Scholar 

  91. C. Rivera, H. Li, J. Thomas-Crusells, H. Lahtinen, T. Viitanen, A. Nanobashvili, Z. Kokaia, M.S. Airaksinen, J. Voipio, K. Kaila and M. Saarma, BDNF-induced TrkB activation down-regulates the K+-Cl-cotransporter KCC2 and impairs neuronal Cl-extrusion, J Cell Biol 159, 747–52 (2002).

    Article  PubMed  CAS  Google Scholar 

  92. C. Rivera, J. Voipio, J. Thomas-Crusells, H. Li, Z. Emri, S. Sipila, J.A. Payne, L. Minichiello, M. Saarma, and K. Kaila, Mechanism of activity-dependent downregulation of the neuron-specific K-Cl cotransporter KCC2, J Neurosci 24, 4683–91 (2004).

    Article  PubMed  CAS  Google Scholar 

  93. F. Aguado, M.A. Carmona, E. Pozas, A. Aguilo, F.J. Martinez-Guijarro, S. Alcantara, V. Borrell, R. Yuste, C.F. and E. Soriano, BDNF regulates spontaneous correlated activity at early developmental stages by increasing synaptogenesis and expression of the K+Cl co-transporter KCC2, Development 130, 1267–80 (2003).

    Article  PubMed  CAS  Google Scholar 

  94. M. Rechsteiner and S.W. Rogers, PEST sequences and regulation by proteolysis, Trends Biochem Sci 21, 267–71 (1996).

    Article  PubMed  CAS  Google Scholar 

  95. V. Vallet, A. Chraibi, H.P. Gaeggeler, J.D. Horisberger and B.C. Rossier, An epithelial serine protease activates the amiloride-sensitive sodium channel, Nature 389, 607–10 (1997).

    Article  PubMed  CAS  Google Scholar 

  96. M. Gu and P.W. Majerus, The properties of the protein tyrosine phosphatase PTPMEG, J Biol Chem 271, 27751–9 (1996).

    Article  PubMed  CAS  Google Scholar 

  97. K. Strange, T.D. Singer, R. Morrison and E. Delpire, Dependence of KCC2 K-Cl cotransporter activity on a conserved carboxy terminus tyrosine residue, Am J Physiol Cell Physiol 279, C860–7. (2000).

    PubMed  CAS  Google Scholar 

  98. A. Mercado, A.H. Enck, K. Zandi-Nejad, G. Gamba and D.B. Mount, Role of the C-terminus of K-Cl cotransporter proteins in volume sensitivity, J Am Soc Nephrol 14, 546A (2003).

    Google Scholar 

  99. S.M. Thompson and B.H. Gahwiler, Activity-dependent disinhibition. II. Effects of extracellular potassium, furosemide, and membrane potential on ECl-in hippocampal CA3 neurons, J Neurophysiol 61, 512–23. (1989).

    PubMed  CAS  Google Scholar 

  100. N.S. Woo, J. Lu, R. England, R. McClellan, S. Dufour, D.B. Mount, A.Y. Deutch, D.M. Lovinger and E. Delpire, Hyperexcitability and epilepsy associated with disruption of the mouse neuronal-specific K-Cl cotransporter gene, Hippocampus 12, 258–68 (2002).

    Article  PubMed  CAS  Google Scholar 

  101. M.F. Karadsheh and E. Delpire, Neuronal restrictive silencing element is found in the kcc2 gene: molecular basis for kcc2-specific expression in neurons, J Neurophysiol 85, 995–7. (2001).

    PubMed  CAS  Google Scholar 

  102. A.N. van den Pol, K. Obrietan and G. Chen, Excitatory actions of GABA after neuronal trauma, J Neurosci 16, 4283–92 (1996).

    PubMed  Google Scholar 

  103. J.A. Coull, D. Boudreau, K. Bachand, S.A. Prescott, F. Nault, A. Sik, P. De Koninck and Y. De Koninck, Trans-synaptic shift in anion gradient in spinal lamina I neurons as a mechanism of neuropathic pain, Nature 424, 938–42 (2003).

    Article  PubMed  CAS  Google Scholar 

  104. J.E. Race, F.N. Makhlouf, P.J. Logue, F.H. Wilson, P.B. Dunham and E.J. Holtzman, Molecular cloning and functional characterization of KCC3, a new K-Cl cotransporter, Am J Physiol 277, C1210–9 (1999).

    PubMed  CAS  Google Scholar 

  105. M.M. Pearson, J. Lu, D.B. Mount and E. Delpire, Localization of the K+-Cl-cotransporter, KCC3, in the central and peripheral nervous systems: expression in the choroid plexus, large neurons and white matter tracts, Neuroscience 103, 481–491. (2001).

    Article  PubMed  CAS  Google Scholar 

  106. O.K. Steinlein, B. Neubauer, T. Sander, L. Song, J. Stoodt and D.B. Mount, Mutation analysis of the potassium-chloride cotransporter KCC3 (SLC12A6) in rolandic and idiopathic generalized epilepsy, Epilepsy Research 44, 191–5 (2001).

    Article  PubMed  CAS  Google Scholar 

  107. S. Kunchaparty, M. Palcso, J. Berkman, H. Velazquez, G.V. Desir, P. Bernstein, R.F. Reilly and D.H. Ellison, Defective processing and expression of thiazide-sensitive Na-Cl cotransporter as a cause of Gitelman’s syndrome, Am J Physiol 277, F643–9 (1999).

    PubMed  CAS  Google Scholar 

  108. N. Dupre, H.C. Howard, J. Mathieu, G. Karpati, M. Vanasse, J.P. Bouchard, S. Carpenter and G.A. Rouleau, Hereditary motor and sensory neuropathy with agenesis of the corpus callosum, Ann Neurol 54, 9–18 (2003).

    Article  PubMed  Google Scholar 

  109. M.R. Shen, C.Y. Chou, K.F. Hsu, H.S. Liu, P.B. Dunham, E.J. Holtzman and J.C. Ellory, KCl cotransporter isoform KCC3 can play an important role in cell growth regulation, Proc Natl Acad Sci U S A 98, 14714–9. (2001).

    Article  PubMed  CAS  Google Scholar 

  110. L. Song, E. Delpire, G. Gamba and D.B. Mount, Localization of the K-Cl cotransporters KCC3 and KCC4 in mouse kidney, FASEB Journal, A341 (2000).

    Google Scholar 

  111. D.B. Mount, L. Song, A. Mercado, A., G. Gamba and E. Delpire, Basolateral localization of renal tubular K-Cl cotransporters, J. Am. Soc. Nephrol. 11, 35A (2000).

    Google Scholar 

  112. K. Ishibashi, F.C. Rector, Jr. and C.A. Berry, Chloride transport across the basolateral membrane of rabbit proximal convoluted tubules, Am J Physiol 258, F1569–78 (1990).

    PubMed  CAS  Google Scholar 

  113. B.C. Kone, H.R. Brady and S.R. Gullans, Coordinated regulation of intracellular K+ in the proximal tubule: Ba2+ blockade down-regulates the Na+,K+-ATPase and up-regulates two K+ permeability pathways, Proc Natl Acad Sci U S A 86, 6431–5 (1989).

    Article  PubMed  CAS  Google Scholar 

  114. M.J. Avison, S.R. Gullans, T. Ogino and G. Giebisch, Na+ and K+ fluxes stimulated by Na+-coupled glucose transport: evidence for a Ba2+-insensitive K+ efflux pathway in rabbit proximal tubules, J Membr Biol 105, 197–205 (1988).

    Article  PubMed  CAS  Google Scholar 

  115. P.A. Welling and M.A. Linshaw, Importance of anion in hypotonic volume regulation of rabbit proximal straight tubule, Am J Physiol 255, F853–60 (1988).

    PubMed  CAS  Google Scholar 

  116. M.G. Cogan, Neurogenic regulation of proximal bicarbonate and chloride reabsorption, Am J Physiol 250, F22–6 (1986).

    PubMed  CAS  Google Scholar 

  117. A. Quan and M. Baum, The renal nerve is required for regulation of proximal tubule transport by intraluminally produced ANG II, Am J Physiol Renal Physiol 280, F524–9 (2001).

    PubMed  CAS  Google Scholar 

  118. N.C. Adragna, R.E. White, S.N. Orlov and P.K. Lauf, K-Cl cotransport in vascular smooth muscle and erythrocytes: possible implication in vasodilation, Am J Physiol 278, C381–390 (2000).

    CAS  Google Scholar 

  119. M. Di Fulvio, P.K. Lauf, S. Shah and N.C. Adragna, NONOates regulate KCl cotransporter-1 and-3 mRNA expression in vascular smooth muscle cells, Am J Physiol Heart Circ Physiol 284, H1686–92 (2003).

    PubMed  Google Scholar 

  120. Y. Chen, M. Morris, E. Delpire, P.K. Lauf and N.C. Adragna, Hypertension in K-Cl cotransporter-3 knockout mice, Faseb J 17, A462 (2003).

    Article  CAS  Google Scholar 

  121. J.W. Meyer, M. Flagella, R.L. Sutliff, J.N. Lorenz, M.L. Nieman, C.S. Weber, R.J. Paul and G.E. Shull, Decreased blood pressure and vascular smooth muscle tone in mice lacking basolateral Na+-K+-2Cl cotransporter, Am J Physiol Heart Circ Physiol 283, H1846–55 (2002).

    PubMed  CAS  Google Scholar 

  122. M.F. Karadsheh, N. Byun, D.B. Mount and E. Delpire, Localization of the KCC4 potassium-chloride cotransporter in the nervous system, Neuroscience 123, 381–91 (2004).

    Article  PubMed  CAS  Google Scholar 

  123. H. Amlal, M. Paillard and M. Bichara, Cl-dependent NH4 + transport mechanisms in medullary thick ascending limb cells, American Journal of Physiology 267, C1607–15 (1994).

    PubMed  CAS  Google Scholar 

  124. A. Mercado, A.H. Enck, K. Zandi-Nejad and D.B. Mount, Functional roles of conserved and variant cysteine residues in the KCC4 K-Cl cotransporter, J Am Soc Nephrol 14 (2003).

    Google Scholar 

  125. R. Estevez, B.C. Schroeder, A. Accardi, T.J. Jentsch and M. Pusch, Conservation of chloride channel structure revealed by an inhibitor binding site in ClC-1, Neuron 38, 47–59 (2003).

    Article  PubMed  CAS  Google Scholar 

  126. E. Delpire, Cation-chloride cotransporters in neuronal communication, News Physiol Sci 15, 309–312 (2000).

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2004 Springer Science+Business Media, Inc.

About this paper

Cite this paper

Mercado, A., Gamba, G., Mount, D.B. (2004). Molecular Physiology of Mammalian K+-CL Cotransporters. 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_3

Download citation

Publish with us

Policies and ethics