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Role of CFTR and Other Ion Channels in Cystic Fibrosis

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Defects of Secretion in Cystic Fibrosis

Part of the book series: Advances in Experimental Medicine and Biology ((volume 558))

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References

  1. J. M. Pilewski and R. A. Frizzell, Role of CFTR in airway disease, Physiol. Rev. 79, S215–S255 (1999).

    PubMed  CAS  Google Scholar 

  2. K. Kunzelmann, The Cystic Fibrosis Transmembrane Conductance Regulator and its function in epithelial transport, Rev. Physiol. Biochem. Pharmacol. 137, 1–70 (1999).

    PubMed  CAS  Google Scholar 

  3. R. C. Boucher, C. U. Cotton, J. T. Gatzy, M. R. Knowles and J. R. Yankaskas, Evidence for reduced Cl− and increased Na+ permeability in cystic fibrosis human primary cell cultures. J. Physiol. (Lond) 405, 77–103 (1988).

    CAS  Google Scholar 

  4. B. R. Grubb and R. C. Boucher, Pathophysiology of gene-targeted mouse models for cystic fibrosis, Physiol Rev. 79, S193–S214 (1999).

    PubMed  CAS  Google Scholar 

  5. K. Kunzelmann, Control of membrane transport by the cystic fibrosis transmembrane conductance regulator (CFTR). In K. L. Kirk and D. C. Dawson, eds., The Cystic Fibrosis Transmembrane Conductance Regulator, Landes Bioscience USA (in press) (2003).

    Google Scholar 

  6. M. M. Reddy and P. M. Quinton, Activation of the epithelial Na+ channel (ENaC) requires CFTR Cl− channel function, Nature 402, 301–304 (1999).

    Article  PubMed  CAS  Google Scholar 

  7. R. C. Boucher, Molecular insights into the physiology of the ‘thin film’ of airway surface liquid. J. Physiol. 516, 631–638 (1999).

    Article  PubMed  CAS  Google Scholar 

  8. M. R. Knowles, M. J. Stutts, A. Spock, N. Fischer, J. T. Gatzy and R. C. Boucher, Abnormal Ion Permeation Though Cystic Fibrosis Respiratory Epithelium, Science 221, 1067–1070 (1983).

    Article  PubMed  CAS  Google Scholar 

  9. T. C. Chinet, J. M. Fullton, J. R. Yankaskas, R. C. Boucher and M. J. Stutts, Mechanism of sodium hyperabsorbtion in cultured cystic fibrosis nasal epithelium: a patch clamp study, Am. J. Physiol. 266, C1061–C1068 (1994).

    PubMed  CAS  Google Scholar 

  10. M. Mall, M. Bleich, R. Greger, R. Schreiber and K. Kunzelmann, The amiloride inhibitable Na+ conductance is reduced by CFTR in normal but not in CF airways, J. Clin. Invest. 102, 15–21 (1998).

    PubMed  CAS  Google Scholar 

  11. H. Matsui, C. W. Davis, R. Tarran and R. C. Boucher, Osmotic water permeabilities of cultured, well-differentiated normal and cystic fibrosis airway epithelia. J. Clin. Invest. 105, 1419–1427 (2000).

    PubMed  CAS  Google Scholar 

  12. J. Zabner, J. J. Smith, P. H. Karp, J. H. Widdicombe and M. J. Welsh, Loss of CFTR chloride channels alters salt absorption by cystic fibrosis airway epithelia in vitro, Mol. Cell 2, 397–403 (1998).

    Article  PubMed  CAS  Google Scholar 

  13. P. M. Quinton, Viscosity versus composition in airway pathology, Am. J. Respir. Crit. Care Med. 149, 6–7 (1994).

    PubMed  CAS  Google Scholar 

  14. R. A. Caldwell, B. R. Grubb, R. Tarran, R. C. Boucher, M. R. Knowles and P. M. Barker, In Vivo Airway Surface Liquid Cl− Analysis with Solid-state Electrodes, J. Gen. Physiol. 119, 3–14 (2002).

    Article  PubMed  CAS  Google Scholar 

  15. R. Tarran, B. R. Grubb, D. Parsons, M. Picher, A. J. Hirsh, C. W. Davis and R. C. Boucher, The CF salt controversy: in vivo observations and therapeutic approaches, Mol. Cell 8, 149–158 (2001).

    Article  PubMed  CAS  Google Scholar 

  16. S. Jayaraman, Y. Song and A. S. Verkman, Airway Surface Liquid Osmolality Measured using Fluorophore-encapsulated Liposomes, J. Gen. Physiol. 117, 423–430 (2001).

    Article  PubMed  CAS  Google Scholar 

  17. J. H. Widdicombe, Regulation of the depth and composition of airway surface liquid, J. Anat. 201, 313–318 (2002).

    Article  PubMed  CAS  Google Scholar 

  18. P. M. Quinton, The neglected ion: HCO3 −, Nat. Med. 7, 292–293 (2001).

    Article  PubMed  CAS  Google Scholar 

  19. M. Mall, T. Gonska, J. Thomas, R. Schreiber, H. H. Seydewitz, J. Kuehr, M. Brandis and K. Kunzelmann, Role of basolateral K+ channels in Ca2+ activated Cl secretion in human normal and cystic fibrosis airway epithelia, Pediatric Research 53, 608–618 (2003).

    Article  PubMed  CAS  Google Scholar 

  20. M. Mall, A. Wissner, R. Schreiber, J. Kühr, H. H. Seydewitz, M. Brandis, R. Greger and K. Kunzelmann, Role of KVLQT1 in cAMP mediated Cl− secretion in human airways, Am. J. Respir. Cell Mol. Biol. 23, 283–289 (2000).

    PubMed  CAS  Google Scholar 

  21. M. Mall, M. Bleich, R. Greger, M. Schürlein, J. Kühr, H. H. Seydewitz, M. Brandis and K. Kunzelmann, Cholinergic ion secretion in human colon requires co-activation by camp, Am. J. Physiol. 275, G1274–G1281 (1998).

    PubMed  CAS  Google Scholar 

  22. M. Bleich, N. Riedemann, R. Warth, D. Kerstan, J. Leipziger, M. Hor, W. V. Driessche and R. Greger, Ca2+ regulated K+ and non-selective cation channels in the basolateral membrane of rat colonic crypt base cells, Pflugers Arch. 432, 1011–1022 (1996).

    Article  PubMed  CAS  Google Scholar 

  23. D. Ecke, M. Bleich and R. Greger, Crypt base cells show forskolin-induced Cl− secretion but no cation inward conductance, Pflugers Arch. 431, 427–434 (1996).

    Article  PubMed  CAS  Google Scholar 

  24. R. Warth and M. Bleich, K+ channels and colonic function, Rev. Physiol. Biochem. Pharmacol. 140, 1–62 (2000).

    PubMed  CAS  Google Scholar 

  25. R. Warth, N. Riedemann, M. Bleich, W. Van Driessche, A. E. Busch and R. Greger, The cAMP-regulated and 293B-inhibited K+ conductance of rat colonic crypt base cells, Pflugers Arch. 432, 81–88 (1996).

    Article  PubMed  CAS  Google Scholar 

  26. D. C. Dawson, Ion channels and colonic salt transport, Ann. Rev. Physiol. 53, 321–339 (1991).

    Article  CAS  Google Scholar 

  27. W. J. Germann, M. E. Lowy, S. A. Ernst and D. C. Dawson, Differentiation of two distinct K conductances in the basolateral membrane of turtle colon, J. Gen. Physiol. 88, 237–251 (1986).

    Article  PubMed  CAS  Google Scholar 

  28. E. Lohrmann, I. Burhoff, R. B. Nitschke, H.-J. Lang, D. Mania, H. C. Englert, M. Hropot, R. Warth, M. Rohm, M. Bleich and R. Greger, A new class of inhibitors of cAMP-mediated Cl− secretion in rabbit colon, acting by the reduction of cAMP-activated K+ conductance, Pflugers Arch. 429, 517–530 (1995).

    Article  PubMed  CAS  Google Scholar 

  29. F. Grahammer, R. Warth, J. Barhanin, M. Bleich, and M. J. Hug, The small conductance K+ channel KCNQ: expression, function and subunit composition in murine trachea, J. Biol Chem. 276, 42268–42275 (2001).

    Article  PubMed  CAS  Google Scholar 

  30. B._C. Schroeder, S. Waldegger, S. Fehr, M. Bleich, R. Warth, R. Greger, and T. J. Jentsch, A constitutional open potassium channel formed by KCNQ1 and KCNE3, Nature 403, 196–199 (2000).

    Article  PubMed  CAS  Google Scholar 

  31. G. Loussouarn, F. Charpentier, R. Mohammad-Panah, K. Kunzelmann, I. Baro, and D. Escande, KvLQT1 potassium channel but not IsK is the molecular target for trans-6-cyano-4-(N-ethylsulfonyl-N-methylamino)-3-hydroxy-2,2-dimethyl-chromane, Mol Pharmacol 52, 1131–1136 (1997).

    PubMed  CAS  Google Scholar 

  32. G. Romey, B. Attali, C. Chouabe, I. Abitbol, E. Guillemare, J. Barhanin, and M. Lazdunski, Molecular mechanism and functional significance of the MinK control of the KvLQTl channel activity, J. Biol. Chem. 272, 16713–16716 (1997).

    Article  PubMed  CAS  Google Scholar 

  33. M. S. Nielsen, R. Warth, M. Bleich, B. Weyand, and R. Greger, The basolateral Ca2+-dependent K+ channel in rat colonic crypt cells, Pflugers Arch. 435, 267–272 (1998).

    Article  PubMed  CAS  Google Scholar 

  34. D. C. Devor and R. A. Frizzell, Modulation of K+ channels by arachidonic acid in T84 cells. I. Inhibition of the Ca2+-dependent K+ channel, Am. J. Physiol 274, C138–C148 (1998).

    PubMed  CAS  Google Scholar 

  35. W. J. Joiner, L. Y. Wang, M. D. Tang, and L. K. Kaczmarek, hSK4, a member of a novel subfamily of calcium-activated potassium channels, Proc. Natl. Acad. Sci. U.S.A. 94, 11013–11018 (1997).

    Article  PubMed  CAS  Google Scholar 

  36. T. M. Ishii, C. Silvia, B. Hirschberg, C. T. Bond, J. P. Adelman, and J. Maylie, A human intermediate conductance calcium-activated potassium channel, Proc. Natl. Acad. Sci. U.S.A. 94, 11651–11656 (1997).

    Article  PubMed  CAS  Google Scholar 

  37. N. J. Logsdon, J. Kang, J. A. Togo, E. P. Christian, and J. Aiyar, A novel gene, hKCa4, encodes the calcium-activated potassium channel in human T lymphocytes, J. Biol. Chem. 272, 32723–32726 (1997).

    Article  PubMed  CAS  Google Scholar 

  38. S. Ghanshani, M. Coleman, P. Gustavsson, A. C. Wu, J. J. Gargus, G. A. Gutman, N. Dahl, H. Mohrenweiser and K. G. Chandy, Human calcium-activated potassium channel gene KCNN4 maps to chromosome 19ql3.2 in the region deleted in diamond-blackfan anemia, Genomics 51, 160–161 (1998).

    Article  PubMed  CAS  Google Scholar 

  39. A. W. Cuthbert, M. E. Hickman, P. Thorn, and L. J. MacVinish, Activation of Ca2+-and cAMP-sensitive K+ channels in murine colonic epithelia by l-ethyl-2-benzimidazolone, Am. J. Physiol 277, C111–C120 (1999).

    PubMed  CAS  Google Scholar 

  40. D. C. Devor, A. K. Singh, R. A. Frizzell, and R. J. Bridges, Modulation of Cl− secretion by benzimidazolones. I. Direct activation of a Ca2+-dependent K+ channel, Am. J. Physiol 271, L775–L784 (1996).

    PubMed  CAS  Google Scholar 

  41. D. C. Devor, A. K. Singh, A. C. Gerlach, R. A. Frizzell and R. J. Bridges, Inhibition of intestinal Cl− secretion by clotrimazole: direct effect on basolateral membrane K+ channels, Am. J. Physiol 273, C531–C540 (1997).

    PubMed  CAS  Google Scholar 

  42. P. A. Rufo, D. Merlin, M. Riegler, M. H. Ferguson-Maltzman, B. L. Dickinson, C. Brugnara, S. L. Alper, and W. I. Lencer, The antifungal antibiotic, clotrimazole, inhibits chloride secretion by human intestinal T84 cells via blockade of distinct basolateral K+conductances. Demonstration of efficacy in intact rabbit colon and in vivo mouse model of cholera, J. Clin. Invest. 100, 3111–3120 (1997).

    PubMed  CAS  Google Scholar 

  43. M. J. Stutts, C. M. Canessa, J. C. Olsen, M. Hamrick, J. A. Cohn, B. C. Rossier, and R. C. Boucher, CFTR as a cAMP-dependent regulator of sodium channels, Science 269, 847–850 (1995).

    Article  PubMed  CAS  Google Scholar 

  44. M. Mall, A. Hipper, R. Greger and K. Kunzelmann, Wild type but not deltaF508 CFTR inhibits Na+ conductance when coexpressed in Xenopus oocytes, FEBS Letters 381, 47–52 (1996).

    Article  PubMed  CAS  Google Scholar 

  45. M. Mall, M. Bleich, J. Kühr, M. Brandis, R. Greger and K. Kunzelmann, CFTR-mediated inhibition of amiloride sensitive sodium conductance by CFTR in human colon is defective in cystic fibrosis, Am. J. Physiol. 277, G709–G716 (1999).

    PubMed  CAS  Google Scholar 

  46. K. Kunzelmann and M. Mall, Electrolyte transport in the colon: Mechanisms and implications for disease, Physiol. Rev. 82, 245–289 (2002).

    PubMed  CAS  Google Scholar 

  47. D. Ecke, M. Bleich, and R. Greger, The amiloride inhibitable Na+ conductance of rat colonic crypt cells is suppressed by forskolin, Pflugers Arch. 431, 984–986 (1996).

    PubMed  CAS  Google Scholar 

  48. I. I. Ismailov, M. S. Awayda, B. Jovov, B. K. Berdiev, C. M. Fuller, J. R. Dedman, M. A. Kaetzel, and D. J. Benos, Regulation of epithelial sodium channels by the cystic fibrosis transmembrane conductance regulator, J. Biol. Chem. 271, 4725–4732 (1996).

    Article  PubMed  CAS  Google Scholar 

  49. P. M. Quinton, Cystic fibrosis: a disease in electrolyte transport, FASEB J. 4, 2709–2717 (1990).

    PubMed  CAS  Google Scholar 

  50. K. Kunzelmann, G. Kiser, R. Schreiber, and J. R. Riordan, Inhibition of epithelial sodium currents by intracellular domains of the cystic fibrosis transmembrane conductance regulator, FEBS Letters 400, 341–344 (1997).

    Article  PubMed  CAS  Google Scholar 

  51. A. Boucherot, R. Schreiber, and K. Kunzelmann, Role of CFTR’s PDZ-binding domain, NBF1 and Cl− conductance in inhibition of epithelial Na+ channels in Xenopus oocytes, Biochim. Biophys. Acta. 1515, 64–71 (2001).

    Article  PubMed  CAS  Google Scholar 

  52. J. König, R. Schreiber, T. Voelcker, M. Mall, and K. Kunzelmann, CFTR inhibits ENaC through an increase in the intracellular Cl− concentration, EMBO Reports 2, 1–5, (2001).

    Article  Google Scholar 

  53. K. Kunzelmann and A. Boucherot. Mechanism of the inhibition of epithelial Na+ channels by CFTR and purinergic stimulation, Kidney International 60, 455–461 (2001).

    Article  PubMed  CAS  Google Scholar 

  54. A. Hopf, R. Schreiber, R. Greger and K. Kunzelmann, CFTR inhibits the activity of epithelial Na+ channels carrying Liddle’s syndrome mutations, J. Biol. Chem. 274, 13894–13899 (1999).

    Article  PubMed  CAS  Google Scholar 

  55. M. Briel, R. Greger, and K. Kunzelmann, Cl− transport by CFTR contributes to the inhibition of epithelial Na+ channels in Xenopus ooyctes coexpressing CFTR and ENaC, J. Physiol. (Lond) 508.3, 825–836 (1998).

    Article  Google Scholar 

  56. A. Dinudom, J. A. Young and D. I. Cook, Na+ and Cl− conductances are controlled by cytosolic Cl− concentration in the intralobular duct cells of mouse mandibular glands, J. Membrane Biol. 135, 289–295 (1993).

    Article  CAS  Google Scholar 

  57. A. Dinudom, P. Komwatana, J. A. Young, and D. I. Cook, Control of the amiloride-sensitive Na+ current in mouse salivary ducts by intracellular anions is mediated by a G protein, J. Physiol. (Lond) 487, 549–555 (1995).

    CAS  Google Scholar 

  58. C. Grygorczyk, H. Chabot, D. H. Malinowska, and J. Cuppoletti, Downregulation of ENaC by ClC-2 chloride channel in Xenopus oocytes, Ped. Pulmonol. Supp. 22, Page (2001).

    Google Scholar 

  59. K. Kunzelmann, ENaC is inhibited by an increase in the intracellular Cl− concentration mediated through activation of Cl− channels, Pflugers Arch. 445, 505–512 (2003).

    Google Scholar 

  60. H. P. Ma, S. Saxena and D. G. Warnock, Anionic phospholipids regulate native and expressed ENaC, J. Biol. Chem. 277, 7641–7644 (2002).

    Article  PubMed  CAS  Google Scholar 

  61. G. Yue, B. Malik and D. C. Eaton, Phosphatidylinositol 4,5-bisphosphate (PIP2) stimulates epithelial sodium channel activity in A6 cells, J. Biol. Chem. 277, 11965–11969 (2002).

    Article  PubMed  CAS  Google Scholar 

  62. N. J. Willumsen and E. H. Larsen, Membrane potentials and intracellular Cl− activity of toad skin epithelium in relation to activation and deactivation of the transepithelial Cl− conductance, J. Membr. Biol. 94, 173–190 (1986).

    Article  PubMed  CAS  Google Scholar 

  63. N. J. Willumsen, C. W. Davis and R. C. Boucher, Intracellular Cl− activity and cellular Cl− pathways in cultured human airway epithelium, Am. J. Physiol. 256, C1033–C1044 (1989).

    PubMed  CAS  Google Scholar 

  64. N. J. Willumsen, C. W. Davis and R. C. Boucher, Cellular Cl− transport in cultured cystic fibrosis airway epithelium, Am. J. Physiol. 256, C1045–C1053 (1989).

    PubMed  CAS  Google Scholar 

  65. N. J. Willumsen and R. C. Boucher, Transcellular sodium transport in cultured cystic fibrosis human nasal epithelium, Am. J. Physiol. 261, C332–C341 (1991).

    PubMed  CAS  Google Scholar 

  66. M. J. Stutts, C. U. Cotton, J. R. Yankaskas, E. Cheng, M. R. Knowles, J. T. Gatzy and R. C. Boucher, Chloride uptake into cultured airway epithelial cells from cystic fibrosis patients and normal individuals, Proc. Natl. Acad. Sci. U.S.A. 82, 6677–6681 (1985).

    Article  PubMed  CAS  Google Scholar 

  67. L. J. Galietta, P. M. Haggie and A. S. Verkman. Green fluorescent protein-based halide indicators with improved chloride and iodide affinities, FEBS Lett. 499, 220–224 (2001).

    Article  PubMed  CAS  Google Scholar 

  68. L. J. Galietta, M. F. Springsteel, M. Eda, E. J. Niedzinski, K. By, M. J. Haddadin, M. J. Kurth, M. H. Nantz and A. S. Verkman, Novel CFTR chloride channel activators identified by screening of combinatorial libraries based on flavone and benzoquinolizinium lead compounds, J. Biol. Chem. 276, 19723–19728 (2001).

    Article  PubMed  CAS  Google Scholar 

  69. S. Jayaraman, P. Haggie, R. M. Wachter, S. J. Remington and A. S. Verkman, Mechanism and cellular applications of a green fluorescent protein-based halide sensor, J. Biol. Chem. 275, 6047–6050 (2000).

    Article  PubMed  CAS  Google Scholar 

  70. M. R. Knowles, L. L. Clarke and R. C. Boucher, Activation by extracellular nucleotides of chloride secretion in the airway epithelia of patients with cystic fibrosis, N. Engl. J. Med. 325, 533–538 (1991).

    Article  PubMed  CAS  Google Scholar 

  71. L. L. Clarke and R. C. Boucher, Chloride secretory response to extracellular ATP in human normal and cystic fibrosis nasal epithelia, Am. J. Physiol. 263, C348–C356 (1992).

    PubMed  CAS  Google Scholar 

  72. L. L. Clarke, T. C. Chinet and R. C. Boucher, Extracellular ATP stimulates K+ secretion across cultured human airway epithelium, Am. J. Physiol. 272, L1084–L1091 (1997).

    PubMed  CAS  Google Scholar 

  73. M. J. Stutts, J. G. Fitz, A. M. Paradiso and R. C. Boucher, Multiple modes of regulation of airway epithelial chloride secretion by ATP, Am. J. Physiol. 267, C1442–C1451 (1994).

    PubMed  CAS  Google Scholar 

  74. H. A. Brown, E. R. Lazarowski, R. C. Boucher and T. K. Harden, Evidence that UTP and ATP regulate phospholipase C through a common extracellular 5′-nucleotide receptor in human airway epithelial cells, Mol. Pharmacol. 40, 648–655 (1991).

    PubMed  CAS  Google Scholar 

  75. I. Butterfield, G. Warhurst, M. N. Jones and G. I. Sandle, Characterization of apical potassium channels induced in rat distal colon during potassium adaptation, J. Physiol. (Lond). 501, 537–547 (1997).

    Article  CAS  Google Scholar 

  76. O. Zegarra-Moran, O. Sacco, L. Romano, G. A. Rossi and L. J. Galietta, Cl− currents activated by extracellular nucleotides in human bronchial cells, J. Membr. Biol. 156, 297–305 (1997).

    Article  PubMed  CAS  Google Scholar 

  77. M. Mall, A. Wissner, J. Kühr, T. Gonska, M. Brandis and K. Kunzelmann, Inhibition of amiloride sensitive epithelial Na+ absorption by extracellular nucleotides in human normal and CF airways, Am. J. Respir. Cell. Mol. Biol. 23, 755–761 (2000).

    PubMed  CAS  Google Scholar 

  78. K. Kunzelmann, R. Schreiber and D. I. Cook, Mechanisms for inhibition of amiloride-sensitive Na+ absorption by extracellular nuceotides in mouse trachea, Pflugers Arch. 444, 220–226 (2002).

    Article  PubMed  CAS  Google Scholar 

  79. D. Communi, P. Paindavoine, G. A. Place, M. Parmentier and J. M. Boeynaems, Expression of P2Y receptors in cell lines derived from the human lung, Br. J. Pharmacol. 127, 562–568 (1999).

    Article  PubMed  CAS  Google Scholar 

  80. E. R. Lazarowski and R. C. Boucher, UTP as an extracellular signaling molecule, News Physiol. Sci. 16, 1–5 (2001).

    PubMed  CAS  Google Scholar 

  81. G. R. Dubyak and C. El-Moatassim, Signal transduction via P2-purinergic receptors for extracellular ATP and other nucleotides, Am. J. Physiol. 265, C577–C606 (1993).

    PubMed  CAS  Google Scholar 

  82. T. H. Hwang, E. M. Schwiebert and W. B. Guggino, Apical and basolateral ATP stimulates tracheal epithelial chloride secretion via multiple purinergic receptors, Am. J. Physiol. 270, C1611–C1623 (1996).

    PubMed  CAS  Google Scholar 

  83. E. R. Lazarowski, A. M. Paradiso, W. C. Watt, T. K. Harden and R. C. Boucher, UDP activates a mucosal-restricted receptor on human nasal epithelial cells that is distinct from the P2Y2 receptor, Proc. Natl. Acad. Sci. U.S.A. 94, 2599–2603 (1997).

    Article  PubMed  CAS  Google Scholar 

  84. E. R. Lazarowski, L. Homolya, R. C. Boucher and T. K. Harden, Direct demonstration of mechanically induced release of cellular UTP and its implication for uridine nucleotide receptor activation, J. Biol. Chem. 272, 24348–24354 (1997).

    Article  PubMed  CAS  Google Scholar 

  85. L. Homolya, T. H. Steinberg and R. C. Boucher. Cell to Cell Communication in Response to Mechanical Stress via Bilateral Release of ATP and UTP in Polarized Epithelia, J. Cell. Biol. 150,1349–1360 (2000).

    Article  PubMed  CAS  Google Scholar 

  86. W. C. Watt, E. R. Lazarowski and R. C. Boucher, Cystic fibrosis transmembrane regulator independent release of ATP. Its implications for the regulation of P2y 2 receptors in airway epithelia, J. Biol. Chem. 273, 14053–14058 (1998).

    Article  PubMed  CAS  Google Scholar 

  87. M. J. Welsh, Effect of phorbol ester and calcium ionophore on chloride secretion in canine tracheal epithelium, Am. J. Physiol. 253, C828–C834 (1987).

    PubMed  CAS  Google Scholar 

  88. M. P. Anderson and M. J. Welsh, Calcium and cAMP activate different chloride channels in the apical membrane of normal and cystic fibrosis epithelia, Proc. Natl. Acad. Sci. U.S.A. 88, 6003–6007 (1991).

    Article  PubMed  CAS  Google Scholar 

  89. K. Kunzelmann, S. Kathöfer and R. Greger. Na+ and Cl− conductances in airway epithelial cells, Increased Na+ conductance in cystic fibrosis, Pflugers Arch. 431, 1–9 (1995).

    Article  PubMed  CAS  Google Scholar 

  90. M. Agnel, T. Vermat and J. M. Culouscou, Identification of three novel members of the calcium-dependent chloride channel (CaCC) family predominantly expressed in the digestive tract and trachea, FEBS Lett. 455, 295–301 (1999).

    Article  PubMed  CAS  Google Scholar 

  91. A. D. Gruber, K. D. Schreur, H. L. Ji, C. M. Fuller and B. U. Pauli, Molecular cloning and transmembrane structure of hCLCA2 from human lung, trachea, and mammary gland, Am. J. Physiol. 276, C1261–C1270 (1999).

    PubMed  CAS  Google Scholar 

  92. Z. Qu, R. W. Wei, W. Mann and H. C. Hartzell, Two bestrophins cloned from Xenopus laevis Oocytes express Ca-activated Cl currents, J. Biol. Chem. 278, 49563–49572 (2003).

    Article  PubMed  CAS  Google Scholar 

  93. H. C. Hartzell and Z. Qu, Chloride currents in acutely isolated Xenopus retinal pigment epithelial cells, J. Physiol 549, 453–469 (2003).

    Article  PubMed  CAS  Google Scholar 

  94. T. Koslowsky, T. Hug, D. Ecke, P. Klein, R. Greger, D. C. Gruenert and K. Kunzelmann, Ca2+ and swelling induced activation of ion conductances in bronchial epithelial cells, Pflugers Arch. 428, 597–603 (1994).

    Article  PubMed  CAS  Google Scholar 

  95. D. C. Devor and J. M. Pilewski, UTP inhibits Na+ absorption in wild-type and DeltaF508 CFTR-expressing human bronchial epithelia, Am. J. Physiol. 276, C827–C837 (1999).

    PubMed  CAS  Google Scholar 

  96. J. Thomas, P. Deetjen, W. H. Ko, C. Jacobi and J. Leipziger, P2y2 receptor-mediated inhibition of amiloride-sensitive short circuit current in m-1 mouse cortical collecting duct cells, J. Membr. Biol 183, 115–124 (2001).

    Article  PubMed  CAS  Google Scholar 

  97. H. Lehrmann, J. Thomas, S. J. Kim, C. Jacobi and J. Leipziger, Luminal P2Y2 receptor-mediated inhibition of Na+ absorption in isolated perfused mouse CCD, J. Am. Soc. Nephrol. 13, 10–18 (2002).

    PubMed  CAS  Google Scholar 

  98. S. K. Inglis, A. Collett, H. L. McAlroy, S. M. Wilson and R. E. Olver, Effect of luminal nucleotides on Cl− secretion and Na+ absorption in distal bronchi, Pflugers Arch. 438, 621–627 (1999).

    Article  PubMed  CAS  Google Scholar 

  99. S. J. Ramminger, A. Collett, D. L. Baines, H. Murphie, H. L. McAlroy, R. E. Olver, S. K. Inglis and S. M. Wilson. P2Y2 receptor-mediated inhibition of ion transport in distal lung epithelial cells, Br. J. Pharmacol. 128, 293–300 (1999).

    Article  PubMed  CAS  Google Scholar 

  100. N. Iwase, T. Sasaki, S. Shimura, M. Yamamoto, S. Suzuki and K. Shirato, ATP-induced Cl− secretion with suppressed Na+ absorption in rabbit tracheal epithelium, Respir. Physiol. 107, 173–180 (1997).

    Article  PubMed  CAS  Google Scholar 

  101. H. P. Ma, L. Li, Z. H. Zhou, D. C. Eaton and D. G. Warnock, ATP masks stretch activation of epithelial sodium channels in A6 distal nephron cells, Am. J. Physiol. 282, F501–F505 (2002).

    CAS  Google Scholar 

  102. D. W. Hilgemann, S. Feng and C. Nasuhoglu, The complex and intriguing lives of PIP2 with ion channels and transporters, Sci. STKE 2001, RE19 (2001).

    Article  PubMed  CAS  Google Scholar 

  103. K. Kunzelmann and M. Mall, Pharmacotherapy of the Ion Transport Defect in Cystic Fibrosis, Potential Role of P2Y2 Receptor Agonists, Am. J. Resp. Med. 2, 299–399 (2003).

    CAS  Google Scholar 

  104. B. Heinke, R. Ribeiro and M. Diener, Involvement of calmodulin and protein kinase C in the regulation of K+ transport by carbachol across the rat distal colon, Eur. J. Pharmacol. 377, 75–80 (1999).

    Article  PubMed  CAS  Google Scholar 

  105. A. K. Singh, D. C. Devor, A. C. Gerlach, M. Gondor, J. M. Pilewski and R. J. Bridges, Stimulation of Cl− secretion by chlorzoxazone, J. Pharmacol Exp. Ther. 292, 778–787 (2000).

    PubMed  CAS  Google Scholar 

  106. H. Garty and L. G. Palmer, Epithelial sodium channels, Function, structure and regulation, Physiol. Rev. 77, 359–396 (1997).

    PubMed  CAS  Google Scholar 

  107. M.R. Knowles, K. N. Olivier, K. W. Hohneker, J. Robinson, W. D. Bennett and R. C. Boucher, Pharmacologic treatment of abnormal ion transport in the airway epithelium in cystic fibrosis, Chest 107, 71S–76S (1995).

    PubMed  CAS  Google Scholar 

  108. R. P. Tomkiewicz, E. M. App, J. G. Zayas, O. Ramirez, N. Church, R. C. Boucher, M. R. Knowles and M. King, Amiloride inhalation therapy in cystic fibrosis. Influence on ion content, hydration, and rheology of sputum, Am. Rev. Respir. Dis. 148, 1002–1007 (1993).

    PubMed  CAS  Google Scholar 

  109. M. R. Knowles, N. L. Church, W. E. Waltner, J. R. Yankaskas, P. Gilligan, M. King, L. J. Edwards, R. W. Helms and R. C. Boucher, A pilot study of aerosolized amiloride for the treatment of lung disease in cystic fibrosis, N. Engl J. Med. 322, 1189–1194 (1990).

    Article  PubMed  CAS  Google Scholar 

  110. A. Graham, A. Hasani, E. W. Alton, G. P. Martin, C. Marriott, M. E. Hodson, S. W. Clarke and D. M. Geddes, No added benefit from nebulized amiloride in patients with cystic fibrosis, Eur. Respir. J. 6, 1243–1248 (1993).

    PubMed  CAS  Google Scholar 

  111. S. Ghosal, C. J. Taylor, W. H. Colledge, R. Ratcliff and M. J. Evans, Sodium channel blockers and uridine triphosphate, effects on nasal potential difference in cystic fibrosis mice, Eur. Respir. J. 15, 146–150 (2000).

    Article  PubMed  CAS  Google Scholar 

  112. W. Pendergast, B. R. Yerxa, J. G. Douglass, S. R. Shaver, R. W. Dougherty, C. C. Redick, I. F. Sims and J. L. Rideout, Synthesis and P2Y receptor activity of a series of uridine dinucleoside 5′-polyphosphates, Bioorg. Med. Chem. Lett. 11, 157–160 (2001).

    Article  PubMed  CAS  Google Scholar 

  113. J. R. Sabater, Y. M. Mao, C. Shaffer, M. K. James, T. G. O’Riordan and W. M. Abraham, Aerosolization of P2Y2-receptor agonists enhances mucociliary clearance in sheep, J. Appl. Physiol. 87, 2191–2196 (1999).

    PubMed  CAS  Google Scholar 

  114. S. D. Guile, F. Ince, A. H. Ingall, N. D. Kindon, P. Meghani and M. P. Mortimore, The medicinal chemistry of the P2 receptor family, Prog. Med. Chem. 38, 115–187 (2001).

    Article  PubMed  CAS  Google Scholar 

  115. D. Mathews, D. Kellerman, J. Gorden, C. Johnson and R. Evans, INS37217, a novel P2Y2 receptor agonist, being developed for the treatment of cystic fibrosis, results from initial phase 1 study in normal volunteers, European Cystic Fibrosis Conference 2001 June 6–9; Vienna, Austria (2002).

    Google Scholar 

  116. P. G. Noone, N. Hamblett, F. Accurso, M. L. Aitken, M. Boyle, M. Dovey, R. Gibson, C. Johnson, D. Kellerman, M. W. Konstan, L. Milgram, J. Mundahl, G. Retsch-Bogort, D. Rodman, J. Williams-Warren, R. W. Wilmott, P. Zeitlin and B. Ramsey, Safety of aerosolized INS 365 in patients with mild to moderate cystic fibrosis, results of a phase I multi-center study, Pediatr. Pulmonol. 32, 122–128 (2001).

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Institut für Physiologie, Universität Regensburg, Universitätstraße 31, D-93053, Regensburg, Germany

    Karl Kunzelmann, Tanja Bachhuber, Gabriele Adam, Thilo Voelcker, Bettina Murle & Rainer Schreiber

  2. Cystic Fibrosis/Pulmonary Research and Treatment Center, School of Medicine, The University of North Carolina at Chapel Hill, 7011 Thurston Bowles Building, Chapel Hill, NC, 27599-7248, USA

    Marcus Mall

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  1. Karl Kunzelmann
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  2. Tanja Bachhuber
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  1. European Molecular Biology Laboratory, Heidelberg, Germany

    Carsten Schultz

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Kunzelmann, K. et al. (2005). Role of CFTR and Other Ion Channels in Cystic Fibrosis. In: Schultz, C. (eds) Defects of Secretion in Cystic Fibrosis. Advances in Experimental Medicine and Biology, vol 558. Springer, Boston, MA. https://doi.org/10.1007/0-387-23250-8_2

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