Advertisement

Regulation of Lymphocyte Chloride Channels

  • Phyllis Gardner
  • Tom McDonald
  • Ikuo Nishimoto
  • John Wagner
  • Muhammad Schumann
  • Jennifer Chen
  • Howard Schulman
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 290)

Abstract

The chloride permeability defect which characterizes the apical membrane of secretory epithelial cells in cystic fibrosis has been difficult to study in part because of lack of accessibility of tissue for study. This problem has fostered attempts by investigators both to immortalize epithelial cell lines and to search for other cells which may serve as a model to study chloride conductances. As we describe here, transformed lympho-blasts have whole cell chloride currents under conditions of stimulation by cAMP agonists, calcium ionophore, or hypotonicity which are quite similar to the aggregate chloride currents measured under similar conditions in epithelial cells. In addition, transformed B and malignant T cells have an outwardly rectifying, 40pS, chloride selective channel that is activated during patch clamp recording by one of at least three ways: 1) patch excision and depolarization; 2) phosphorylation by cAMP-dependent protein kinase (PKA); 3) by exposure of the lympho-blast to Ca2+ ionophore during cell-attached recording. This channel is closely similar or identical to the outwardly rectifying chloride channel identified by patch clamp recording from the apical membrane in secretory epithelial cells (Frizzell et al., 1986; Welsh, 1986; Welsh and Liedtke, 1986; Schoumacher et al., 1987; Li et al., 1988).

Keywords

Cystic Fibrosis Chloride Channel Calcium Ionophore Patch Clamp Recording Secretory Epithelial Cell 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Beavo, J.A., Bechtel, P.J. and Krebs, E.G., 1975, Activation of protein kinase by physiological concentrations of cyclic AMP, Methods Enzymol., 38:299.CrossRefGoogle Scholar
  2. Chen, J.H., Schulman, H. and Gardner P., 1989, A c-AMP regulated chloride channel in lymphocytes that is affected in cystic fibrosis, Science, 243:657.PubMedCrossRefGoogle Scholar
  3. Frizzell, R.A., Rechkemmer, G. and Shoemaker, R.L., 1986, Altered regulation of airway epithelial cell chloride channels in cystic fibrosis, Science, 232:558.CrossRefGoogle Scholar
  4. Hamill, O.P., Marty, A., Neher, E., Sakmann, B. and Sigworth, F.J., 1981, Improved patch-clamp techniques for high-resolution current recordings from cells and cell-free membrane patches, Pfluegers Arch., 391:85.CrossRefGoogle Scholar
  5. 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 in cystic fibrosis airway epithelium, Nature, 331:358.PubMedCrossRefGoogle Scholar
  6. 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.PubMedCrossRefGoogle Scholar
  7. Malinow, R., Schulman, H. and Tsien, R.W., 1989, Inhibition of postsynaptic PKC or CamMKII blocks induction but not expression of LTP, Science, 245:862.PubMedCrossRefGoogle Scholar
  8. 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, 330:752.PubMedCrossRefGoogle Scholar
  9. Schulman, H. J., 1984, Phosphorylation of microtube-associated proteins by a Ca2+/calmodulin dependent protein kinase, Cell Biol., 99:19.CrossRefGoogle Scholar
  10. Welsh, M.J., 1986, An apical-membrane chloride channel in human tracheal epithelium, Science, 23 2:1648.CrossRefGoogle Scholar
  11. Welsh, M.J. and Liedtkec C.M., 1986, Chloride and potassium channels in cystic fibrosis epithelia, Nature, 3 22:467.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1991

Authors and Affiliations

  • Phyllis Gardner
  • Tom McDonald
  • Ikuo Nishimoto
  • John Wagner
  • Muhammad Schumann
  • Jennifer Chen
  • Howard Schulman

There are no affiliations available

Personalised recommendations