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Outwardly rectifying chloride channels and CF: A divorce and remarriage

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Abstract

Outwardly rectifying Cl− channels were originally thought to be the central element in cystic fibrosis. The role of these channels in CF was questioned to such an extent that doubts were rasied about the validity of the original experiments. Recent data reestablishes a role for outwardly rectifying Cl− channels (ORCC) in CF and suggests that the protein encoded by the CF gene, the cystic fibrosis transmembrane regulator (CFTR), can effect the regulation of more than one channel in the airway. This minireview deals with the rise, fall, and resurrection of the role of outwardly rectifying Cl− channels in CF.

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References

  • Anderson, M. P., and Welsh, M. J. (1990). Fatty acids inhibit apical membrane chloride channels in airway epithelia,Proc. Natl. Acad. Sci. USA 87, 7334–7338.

    Google Scholar 

  • Anderson, M. P., Gregory, R. J., Thompson, S., Souza, D. W., Paul, S., Mulligan, R. C., Smith, A.E., and Welsh, M. J. (1991a). Demonstration that CFTR is a chloride channel by alteration of its anion selectivity,Science 253, 202–205.

    Google Scholar 

  • Anderson, M. P., Rich, D. P., Gregory, R. J., Smith, A. E., and Welsh, M. J. (1991). Generation ofcAMP-activated chloride currents by expression of CFTR,Science 251, 679–682.

    Google Scholar 

  • Barasch, J., Kiss, B., Prince, A., Saiman, L., Gruenert, D.C., and Al-Awqati, Q. (1991). Defective acidification of intracellular organelles in cystic fibrosis,Nature (London)352, 70–73.

    Google Scholar 

  • Bear, C. E., Duguay, F., Naismith, A. L., Kartner, N., Hanrahan, J. W., and Riordan, J. R. (1991). Cl− channel activity inXenopus oocytes expressing the cystic fibrosis gene,J. Biol. Chem. 266, 19142–19145.

    Google Scholar 

  • Bear, C. E., Li, C., Kartner, N., Bridges, R. J., Jensen, T. J., Ramjeesingh, M., and Riordan, J. R. (1992). Purification and functional reconstitution of the cystic fibrosis transmembrane conductance regulator (CFTR).Cell 68, 809–818.

    Google Scholar 

  • Chen, J. H., Schulman, H., and Gardner, P. (1989). AcAMP-regulated chloride channel in lymphocytes that is affected in cystic fibrosis,Science 243, 657–660.

    Google Scholar 

  • Clarke, L. L., Grubb, B. R., Gabriel, S. E., Smithies, O., Koller, B. H., and Boucher, R. C. (1992). Defective epithelial chloride transport in a gene-targeted mouse model of cystic fibrosis,Science 257, 1125–1128.

    Google Scholar 

  • Cliff, W. H., and Frizzell, R. A. (1990). Separate Cl− coductances activated bycAMP and Ca in Cl-secreting epithelial cells,Proc. Natl. Acad. Sci. USA 87, 4956–4960.

    Google Scholar 

  • Collins, F. S. (1992). Cystic fibrosis: molecular biology and theraputic implications,Science 256, 774–779.

    Google Scholar 

  • Dalemans, W., Barby, P., Champigny, G. Jallat, S., Dott, K., Dreyer, D., Crystal, R. G. Pavirani, A., Lecocq, J.-P., and Lazdunski, M. (1992). Altered chloride ion channel kinetics associated with the ΔF508 cystic fibrosis mutation,Nature (London)354, 526–528.

    Google Scholar 

  • Drumm, M. L., Pope, H. A., Cliff, W. H., Rommens, J. M., Marvin, S. A., Tsui, L. C., Collins, F. S., Frizzell, R. A., and Wilson, J. M. (1990). Correction of the cystic fibrosis defectin vitro by retrovirus-mediated gene transfer,Cell 62, 1227–1233.

    Google Scholar 

  • Drumm, M. L., Wilkinson, D. J., Smit, W. S., Worrell, R. T., Strong, T. V., Frizzell, R. A., Dawson, D. C., and Collins, F. S. (1992). Chloride conductance expressed by delF508 and other mutant CFTRs inXenopus oocytes,Science 254, 1797–1799.

    Google Scholar 

  • Egan, M., Flotte, T., Afione, S., Solow, R., Zeitlin, P. L., Carter, B. J., and Guggino, W. B. (1992). Defective regulation of outwardly rectifying Cl− channels by protein kinase A corrected by insertion of CFTR,Nature (London)358, 581–584.

    Google Scholar 

  • Frizzell, R. A., Halm, D. R., Rechkemmer, G., and Shoemaker, R. L. (1986a). Chloride channel regulation in secretory epithelia,Fed. Proc. 45, 2727–2731.

    Google Scholar 

  • Frizzell, R. A., Rechkemmer, G., and Shoemaker, R. L. (1986b). Altered regulation of airway epithelial cell chloride channels in cystic fibrosis,Science 233, 558–560.

    Google Scholar 

  • Garber, S. S. (1992). Outwardly rectifying chloride channels in lymphocytes,J. Membr. Biol. 127, 49–56.

    Google Scholar 

  • Gray, M. A., Harris, A., Coleman, L., Greenwell, J. R., and Argent, B. E. (1989). Two types of chloride channel on duct cells cultured from human fetal pancreas,Am. J. Physiol 257, C240-C251.

    Google Scholar 

  • Gregory, R. J., Cheng, S. H., Rich, D. P., Marshall, J., Paul, S., Hehir, K., Ostedgaard, L., Klinger, K. W., Welsh, M. J., and Smith, A.E. (1990). Expression and characterization of the cystic fibrosis transmembrane conductance regulator, [see comments],Nature 347, 382–386.

    Google Scholar 

  • Hagiwara, G., Krouse, M., Muller, U., and Wine, J. (1989). Is regulation of a chloride channel in lymphocytes affected in cystic fibrosis? [letter, comment],Science 246, 1049–1050.

    Google Scholar 

  • Halm, D. R., Rechkemmer, G. R., Schoumacher, R. A., and Frizzell, R. A. (1988). Apical membrane chloride channels in a colonic cell line activated by secretory agonists,Am. J. Physiol. 254, C505-C511.

    Google Scholar 

  • Hanrahan, J. W., and Tabcharani, J. A. (1990). Inhibition of outwardly rectifying anion channel by HEPES and related buffers,J. Membr. Biol. 116, 65–77.

    Google Scholar 

  • Hayslett, J. P., Gogelein, H., Kunzelmann, K., and Greger, R. (1987). Characteristics of apical chloride channels in human colon cells (HT29),Pfluegers Arch. 410, 487–494.

    Google Scholar 

  • Hoshi, T., Zagotta, W. N., and Aldrich, W. (1990). Biophysical and molecular mechanisms of shaker potassium channel inactivation,Science 250, 533–538.

    Google Scholar 

  • Hwang, T.-C., Lu, L., Zeitlin, P. L., Gruenert, D. C., Huganir, R., and Guggino, W. B. (1989). Chloride channels in CF: Lack of activation by protein kinase C andcAMP-dependent protein kinase,Science 244, 1351–1353.

    Google Scholar 

  • Hwang, T.-C., Guggino, S. E., and Guggino, W. B. (1990). Direct modulation of secretory chloride channels by arachidonic and othercis-unsaturated fatty acids,Proc. Natl. Acad. Sci. USA 87, 5706–5709.

    Google Scholar 

  • Hwang, T.-C., Egan, M. E., and Guggino, W. B. (1992). Kinetic interaction of fatty acids with outwardly rectifying chloride channels,Cell. Physiol. Biochem., in press.

  • Kartner, N., Hanrahan, J. W. Jensen, T. J., Naismith, A. L., Sun, S. Z., Ackerley, C. A., Reyes, E. F., Tsui, L. C. Rommens, J. M., and Bear, C. E. (1991). Expression of the cystic fibrosis gene in non-epithelial invertebrate cells produces a regulated anion conductance,Cell 64, 681–691.

    Google Scholar 

  • Krick, W., Disser, J., Hazama, A., Burckhardt, G., and Fromter, E. (1991). Evidence for a cytosolic inhibitor of epithelial chloride channels,Pfluegers Arch. 418, 491–499.

    Google Scholar 

  • Krouse, M. E., Hagiwara, G., Chen, J., Lewiston, N. J., and Wine, J. J. (1989). Ion channels in normal human and cystic fibrosis sweat gland cells,Am. J. Physiol 257, C129-C140.

    Google Scholar 

  • Kunzelmann, K., Pavenstadt, H., and Greger, R. (1989). Properties and regulation of chloride channels in cystic fibrosis and normal airway cells,Pfluegers Arch. 415, 172–182.

    Google Scholar 

  • Kunzelmann, K., Tilmann, M., Hansen, C. P., and Greger, R. (1991). Inhibition of epithelial chloride channels by cytosol,Pfluegers Arch. 418, 479–490.

    Google Scholar 

  • Li, M., McCann, J. D.., Liedtke, C. M., Nairn, A. C., Greengard, P., and Welsh, M. J. (1988). Cyclic AMP-dependent protein kinase opens chloride channels in normal but not cystic fibrosis airway epithelium,Nature 331, 358–360.

    Google Scholar 

  • Li, M., McCann, J. D., Anderson, M. P., Clancy, J. P., Liedtke, C. M., Nairn, A. C., Greengard, P., and Welsh, M. J. (1989). Regulation of chloride channels by protein kinase C in normal and cystic fibrosis airway epithelia,Science 244, 1353–1356.

    Google Scholar 

  • Lin, M., Nairn, A. C., and Guggino, S. W. (1992). CAMP-dependent protein kinase regulation of a chloride channel in T84 cells,Am. J. Physiol. Cell Physiol. 262, C1304-C1312.

    Google Scholar 

  • Oberleithner, H., Ritter, M., Lang, F., and Guggino, W. B. (1983). Antracene-9-carboxylic acid inhibits renal chloride reabsorption,Pfluegers Arch. 398, 172–174.

    Google Scholar 

  • Quinton, P. M. (1983). Chloride impermeability in cystic fibrosis,Nature (London)301, 421–422.

    Google Scholar 

  • Reisin, I. L., Prat, A. G., Abraham, E. H., Amara, J., Gregory, R., Ausiello, D. A., and Cantiello, H. F. (1992). Expression of CFTR results in the appearance of an ATP channel,J. Gen. Physiol. 100, 33a.

  • Riordan, J. R., Rommens, J. M., Kerem, B.-S., Alon, N., Rozmahel, R. Grezelczak, Z., Zielenski, J., Lok, S., Plavsic, N., Chou, J.-L., Drumm, M. L., Iannuzzi, M. C., Collins, F. S., and Tsui, L.-C. (1989). Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA,Science 245, 1066–1073.

    Google Scholar 

  • Rommens, J. M., Iannuzzi, M. C., Kerem, B.-S., Drumm, M. L., Melmer, G., Dean, M., Rozmahel, R., Cole, J. L., Kennedy, D., Hidaka, N., Zsiga, M., Buckwald, M., Riordan, J. R., Tsui, L.-C., and Collins, F. S. (1989). Identification of the cystic fibrosis gene: chromosome walking and jumping,Science 245, 1059–1065.

    Google Scholar 

  • Schoumacher, R. A., Shoemaker, R. L., Halm, D. R., Tallant, E. A., Wallace, R. W., and Frizzell, R. A. (1987). Phosphorylation fails to activate chloride channels from cystic fibrosis airway cells,Nature (London)330, 752–754.

    Google Scholar 

  • Singh, A. K., Afink, G. B., Venglarik, C. J., Wang, R., and Bridges, R. J. (1991). Colonic Cl channel blockade by three classes of compounds,Am. J. Physiol. 260, C51-C63.

    Google Scholar 

  • Solc, C. K., and Wine, J. J. (1991). Swelling-induced and depolarization-induced Cl− channels in normal and cystic fibrosis epithelial cells,Am. J. Physiol. 261, C658-C674.

    Google Scholar 

  • Sorscher, E. J., Bridges, R. J., Fuller, C. M., Frizzell, R. A., and Benos, D. J. (1989). Antibodies to a synthetic DIDS-binding peptide inhibit colonic secretory chloride channels and identify a 60-kDa protein as a component of the channel complex,Ped. Pulm. Suppl. 4, 102–103 (Abstract).

    Google Scholar 

  • Stutts, M. J., Chinet, T. C., Mason, S. J., Fullton, J. M., Clarke, L. L., and Boucher, R. C. (1992). Regulation of Cl− channels in normal and cystic fibrosis airway epithelial cells by extracellular ATP,Proc. Natl. Acad. Sci. USA 89, 1621–1625.

    Google Scholar 

  • Tabcharani, J. A., and Hanrahan, J. W. (1991). On the activation of outwardly rectifying anion channels in excised patches,Am. J. Physiol. Gastrointest. Liver Physiol. 261, G992-G999.

    Google Scholar 

  • Valverde, M. A. Díaz, M., Sepúlveda, F. V., Gill, D. R., Hyde, S. C., and Higgins, C. F. (1992). Volume-regulated chloride channels associated with the human multidrug-resistance P-glycoprotein,Nature (London)355, 830–833.

    Google Scholar 

  • Wagner, J. A., Cozens, A. L., Schulman, H., Gruenert, D. C. Stryer, L., and Gardner, P. (1991). Activation of chloride channels in normal and cystic fibrosis airway epithelial cells by multifunctional calcium/calmodulin-dependent protein kinase,Nature (London)349, 793–796.

    Google Scholar 

  • Ward, C. L., Krouse, M. E., Gruenert, D. C., Kopito, R. R., and Wine, J. J. (1991). Cystic fibrosis gene expression is not correlated with rectifying Cl− channels,Proc. Natl. Acad. Sci. USA 88, 5277–5281.

    Google Scholar 

  • Welsh, M. J. (1986). An apical-membrane chloride channel in human tracheal epithelium,Science 232, 1648–1650.

    Google Scholar 

  • Welsh, M. J., and Liedtke, C. M. (1986). Chloride and potassium channels in cystic fibrosis airway epithelia,Nature (London)322, 467–470.

    Google Scholar 

  • Welsh, M. J., Li, M., and McCann, J. D. (1989). Activation of normal and cystic fibrosis Cl− channels by voltage, temperature, and trypsin,J. Clin. Invest. 84, 2002–2007.

    Google Scholar 

  • Zagotta, W. N., Hoshi, T., and Aldrich, W. (1990). Restoration of inactivation in mutants of shaker potassium channels by a peptide derived from ShB,Science 250, 568–571.

    Google Scholar 

  • Zeitlin, P. L., Lu, L., Rhim, J., Cutting, G. Stetten, G., Kieffer, K. A. Craig, R., and Guggino, W. B. (1991). A cystic fibrosis bronchial epithelial cell line: immortalization by adeno-12-SV40 infection,Am. J. Respir. Cell Mol. Biol. 4, 313–331.

    Google Scholar 

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  1. Johns Hopkins University School of Medicine, 725 North Wolfe Street, 21205, Baltimore

    William B. Guggino (Associate Professor of Physiology and Pediatrics)

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  1. William B. Guggino
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Guggino, W.B. Outwardly rectifying chloride channels and CF: A divorce and remarriage. J Bioenerg Biomembr 25, 27–35 (1993). https://doi.org/10.1007/BF00768065

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