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ABSTRACT CYSTIC fibrosis (CF) is a lethal genetic disease resulting in a reduced CI− permeability1, increased mucous sulphation2, increased Na+ absorption3 and defective acidification of
lysosomal vesicles4. The CF gene encodes a protein (the cystic fibrosis trans-membrane conductance regulator, CFTR5) that can function as a low-conductance Cl− channel with a linear
current-voltage relationship whose regulation is defective in CF patients6–8. Larger conductance, outwardly rectifying Cl− channels are also defective in CF and fail to activate when exposed
either to cyclic AMP-dependent protein kinase A or to protein kinase C9–13. The role of the outwardly rectifying Cl− channel in CF has been questioned14. We report here that expression of
recombinant CF genes using adeno-associated virus vectors in CF bronchial epithelial cells corrects defective Cl− secretion, that it induces the appearance of small, linear conductance Cl−
channels, and restores protein kinase A activation of outwardly rectifying Cl− channels. These results re-establish an involvement of outwardly rectifying Cl− channels in CF and suggest that
CFTR regulates more than one conductance pathway in airway tissues. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution
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about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS CYSTIC FIBROSIS Article 08 August 2024 SFPQ RESCUES F508DEL-CFTR
EXPRESSION AND FUNCTION IN CYSTIC FIBROSIS BRONCHIAL EPITHELIAL CELLS Article Open access 17 August 2021 GENE-SPECIFIC NONSENSE-MEDIATED MRNA DECAY TARGETING FOR CYSTIC FIBROSIS THERAPY
Article Open access 27 May 2022 REFERENCES * Frizzell, R. A. _Trends Neurosci._ 10, 190–193 (1987). Article CAS Google Scholar * Cheng, P. W. _et al._ _J. clin. Invest._ 84, 68–72 (1989).
Article ADS CAS Google Scholar * Quinton, P. M. _FASEB J._ 4, 2709–2717 (1990). Article CAS Google Scholar * Barasch, J. _et al._ _Nature_ 352, 70–73 (1991). Article ADS CAS
Google Scholar * Riordin, J. R. _et al._ _Science_ 245, 1066–1073 (1989). Article ADS Google Scholar * Kartner, N. _et al._ _Cell_ 64, 681–691 (1991). Article CAS Google Scholar *
Anderson, M. P. _et al._ _Science_ 253, 202–205 (1991). Article ADS CAS Google Scholar * Bear, C. E. _et al._ _J. biol. Chem._ 266, 19142–19145 (1991). CAS PubMed Google Scholar * Li,
M. _et al._ _Nature_ 331, 358–360 (1988). Article ADS CAS Google Scholar * Li, M. _et al._ _Science_ 244, 1353–1356 (1989). Article ADS CAS Google Scholar * Schoumacher, R. A. _et
al._ _Nature_ 330, 752–754 (1987). Article ADS CAS Google Scholar * Chen, J. H., Schulman, H. & Gardner, P. _Science_ 243, 657–660 (1989). Article ADS CAS Google Scholar * Hwang,
T. C. _et al._ _Science_ 244, 1351–1353 (1989). Article ADS CAS Google Scholar * Ward, C. L. _et al._ _Proc. natn. Acad. Sci. U.S.A._ 88, 5277–5281 (1991). Article ADS CAS Google
Scholar * Zeitlin, P. L. _et al._ _Am. J. respir. Cell molec. Biol._ 4, 313–319 (1991). Article CAS Google Scholar * Flotte, T. R. _et al._ _Am. J. respir. Cell molec. Biol._ (in the
press). * Rich, D. P. _et al._ _Nature_ 347, 358–363 (1990). Article ADS CAS Google Scholar * Drumm, M. L. _et al._ _Cell_ 62, 1227–1233 (1990). Article CAS Google Scholar * Anderson,
M. P. _et al._ _Cell_ 67, 775–784 (1991). Article CAS Google Scholar * Bridges, R. J., Worrell, R. T., Frizzell, R. A. & Benos, D. J. _Am. J. Physiol._ 2562, C902–C912 (1989).
Article Google Scholar * Anderson, M. P. & Welsh, M. J. _Proc. natn. Acad. Sci. U.S.A._ 88, 6003–6007 (1991). Article ADS CAS Google Scholar * Welsh, M. J., Li, M. & McCann, J.
D. _J. clin. Invest._ 84, 2002–2007 (1989). Article CAS Google Scholar * Zeitlin, P. L. _et al._ _Proc. natn. Acad. Sci. U.S.A._ 89, 344–347 (1992). Article ADS CAS Google Scholar *
Trapnell, B. C. _et al._ _J. biol. Chem._ 266, 10319–10323 (1991). CAS PubMed Google Scholar * Flotte, T. _et al._ _Ped. Pulm._ 6 (suppl.) 247 (1991). Google Scholar Download references
AUTHOR INFORMATION Author notes * William B. Guggino: To whom correspondence should be addressed. AUTHORS AND AFFILIATIONS * Departments of Physiology and Pediatrics, Johns Hopkins
University School of Medicine, Baltimore, Maryland, 21205, USA Marie Egan, Terence Flotte, Pamela L. Zeitlin & William B. Guggino * Laboratory of Molecular and Cellular Biology, National
Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA Terence Flotte, Sandra Afione, Rikki Solow & Barrie J. Carter Authors *
Marie Egan View author publications You can also search for this author inPubMed Google Scholar * Terence Flotte View author publications You can also search for this author inPubMed Google
Scholar * Sandra Afione View author publications You can also search for this author inPubMed Google Scholar * Rikki Solow View author publications You can also search for this author
inPubMed Google Scholar * Pamela L. Zeitlin View author publications You can also search for this author inPubMed Google Scholar * Barrie J. Carter View author publications You can also
search for this author inPubMed Google Scholar * William B. Guggino View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and
permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Egan, M., Flotte, T., Afione, S. _et al._ Defective regulation of outwardly rectifying Cl− channels by protein kinase A corrected by
insertion of CFTR. _Nature_ 358, 581–584 (1992). https://doi.org/10.1038/358581a0 Download citation * Received: 29 April 1992 * Accepted: 25 June 1992 * Issue Date: 13 August 1992 * DOI:
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