Conductance Pathways Involved in Chloride Secretion and Their Regulation

  • William H. Cliff
  • Roger T. Worrell
  • Andrew P. Morris
  • Raymond A. Frizzell
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 290)


Cystic fibrosis impairs the secretory activities of a variety of exocrine glands and other secretory epithelia in the intestines and airways. The secretion of salt and water across epithelia of this type is driven by a secondary active Cl transport mechanism (Frizzell et al., 1979). Chloride enters secretory cells due to the combined activities of three basolateral membrane transport events: Na/K/Cl co-transporters, Na/K pumps, and K channels. Chloride leaves secretory cells across the apical membranes by diffusion, and alterations in apical Cl conductance represent a pivotal control point that determines Cl secretion rate. A variety of hormones and neurotransmitters stimulate salt secretion via their intracellular mediators, cAMP and Ca. The overall Cl secretory process is electrogenic so that the co-ion, Na, accompanies Cl to the lumen via paracellular pathways, driven by the lumen-negative voltage arising from Cl secretion.


Cystic Fibrosis Cystic Fibrosis Airway Outward Rectification Secretory Epithelial Cell Outward Rectifier 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. Bahinski, A., A.C. Nairn, P. Greengard, and D.C. Gadsby, 1989, Chloride conductance regulated by cyclic AMP-dependent protein kinase in cardiac myocytes, Nature 340:718.PubMedCrossRefGoogle Scholar
  2. Cliff, W.H., and R.A. Frizzell, 1990, Separate Cl conduct ances activated by cAMP and Ca in Cl-secreting epithelial cells, Proc. Natl. Acad. Sci. USA, in press.Google Scholar
  3. Evans, M.G., and A. Marty, 1986, Calcium-dependent chloride currents in isolated cells from rat lacrimal glands, J. Physiol. 378:437.PubMedGoogle Scholar
  4. Frizzell, R.A., 1987, Cystic fibrosis: A disease of ion channels? Trends in Neurosci. 10:190.CrossRefGoogle Scholar
  5. Frizzell, R.A., M. Field, and S.G. Schultz, 1979, Sodium-coupled chloride transport by epithelial tissues, Am. J. Physiol. 236:F1.PubMedGoogle Scholar
  6. Frizzell, R.A., G.R. Rechkemmer, and R.L. Shoemaker, 1986, Altered regulation of airway epithelial cell chloride channels in cystic fibrosis, Science 23 3:558.CrossRefGoogle Scholar
  7. Giraldez, F., K.J. Murray, F.V. Sepulveda, and D.N. Sheppard, 1989, Characterization of a phosphorylation-activated Cl--selective channel in isolated Necturus enterocytes, J. Physiol. 416:517.PubMedGoogle Scholar
  8. Gray, M.A., A. Harris, L. Coleman, J.R. Greenwell, and B.E. Argent, 1989, Two types of chloride channel on duct cells cultured from human fetal pancreas, Am. J. Physiol. 257:C240.PubMedGoogle Scholar
  9. Halm, D.R., G.R. Rechkemmer, R.A. Schoumacher, and R.A. Frizzell, 1988, Apical membrane chloride channels in a colonic cell line activated by secretory agonists, Am. J. Physiol. 254:C505.PubMedGoogle Scholar
  10. Harvey, R.D., and J.R. Hume, 1989, Autonomic regulation of a chloride current in heart, Science 244:983.PubMedCrossRefGoogle Scholar
  11. Hoffmann, E.K., I.H. Lambert, and L.O. Simonsen, 1986, Separate Ca2+ activated K and Cl transport pathways in Ehrlich ascites tumor cells, J. Membr. Biol. 91:227.PubMedCrossRefGoogle Scholar
  12. Hwang, T.-C, L. Lu, P.L. Zeitlin, D.C. Gruenert, R. Huganir, and W.B. Guggino, 1989, Cl channels in CF: Lack of activation by protein kinase C and cAMP-dependent protein kinase, Science 244:1351.PubMedCrossRefGoogle Scholar
  13. Li, M., J.D. McCann, M.P. Anderson, J.P. Clancy, C.M. Liedtke, A.C. Nairn, P. Greengard, and M.J. Welsh, 1989, Regulation of Chloride channels by protein kinase C in normal and cystic fibrosis airway epithelia, Science 244:1353.PubMedCrossRefGoogle Scholar
  14. Li, M., J.D. McCann, C.M. Liedtke, A.C. Nairn, P. Greengard, and M.J. Welsh, 1988, Cyclic AMP-dependent protein kinase opens chloride channels in normal but not cystic fibrosis airway epithelium, Nature 331:358.PubMedCrossRefGoogle Scholar
  15. McCann, J.D., M. Li, and M.J. Welsh, 1989. Identification and regulation of whole-cell chloride currents in airway epithelium, J. Gen. Physiol. 94:1015.PubMedCrossRefGoogle Scholar
  16. Penner, R., G. Matthews, and E. Neher, 1988, Regulation of calcium influx by second messengers in rat mast cells, Nature 334:499.PubMedCrossRefGoogle Scholar
  17. Schoppa, N., S.R. Shorofsky, F. Jow, and D.J. Nelson, 1989, Voltage-gated chloride currents in cultured canine tracheal epithelial cells, J. Membr. Biol. 108:73.PubMedCrossRefGoogle Scholar
  18. Schoumacher, R.A., R.L. Shoemaker, D.R. Halm, E.A. Tallant, R.W. Wallace, and R.A. Frizzel, 1987, Phosphorylation fails to activate chloride channels from cystic fibrosis airway cells, Nature 330:752.PubMedCrossRefGoogle Scholar
  19. Shoemaker, R.L., R.A. Frizzell, T.M. Dwyer, and J.M. Farley, 1986. Single-channel currents from canine tracheal epithelial cells, Biochem. Biophys. Acta 858:235.PubMedCrossRefGoogle Scholar
  20. Worrell, R.T., A.G. Butt, W.J. Cliff, and R.A. Frizzell, 1989, A volume-sensitive chloride conductance in the human colonic cell line, T84, Am. J. Physiol. 256:C1111.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1991

Authors and Affiliations

  • William H. Cliff
    • 1
  • Roger T. Worrell
    • 1
  • Andrew P. Morris
    • 1
  • Raymond A. Frizzell
    • 1
  1. 1.Department of Physiology and Biophysics, Gregory Fleming James Cystic Fibrosis Research CenterUniversity of Alabama at BirminghamBirminghamUSA

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