Cyclic AMP-dependent protein kinase opens chloride channels in normal but not cystic fibrosis airway epithelium (original) (raw)
- Letter
- Published: 28 January 1988
- John D. McCann1,
- Carole M. Liedtket2,
- Angus C. Nairn3,
- Paul Greengard3 &
- …
- Michael J. Welsh1 na1
Nature volume 331, pages 358–360 (1988)Cite this article
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Abstract
Chloride (Cl–) secretion by the airway epithelium regulates, in part, the quantity and composition of the respiratory tract fluid, thereby facilitating mucociliary clearance. The rate of Cl– secretion is controlled by apical membrane Cl– channels1. Apical Cl– channels are opened and Cl– secretion is stimulated by a variety of hormones and neurotransmitters that increase intracellular levels of cyclic AMP (cAMP)1–2. In cystic fibrosis (CF), a common lethal genetic disease of Caucasians, airway3,4, sweat-gland duct5, secretory-coil6 and possibly other epithelia7 are anion impermeable. This abnormality may explain several of the clinical manifestations of the disease. The Cl– impermeability in CF-airway epithelia has been localized to the apical cell membrane4, where regulation of Cl– channels is abnormal8,9: hormonal secretagogues stimulate cAMP accumulation appropriately but Cl– channels fail to open. Here we report that the purified catalytic subunit of cAMP-dependent protein kinase plus ATP opens Cl– channels in excised, cell-free patches of membrane from normal cells, but fails to open Cl–; channels in CF cells. These results indicate that in normal cells, the cAMP-dependent protein kinase phosphorylates the Cl– channel or an associated regulatory protein, causing the channel to open. The failure of CF Cl– channels to open suggests a defect either in the channel or in such an associated regulatory protein.
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Author notes
- Michael J. Welsh: To whom correspondence should be addressed.
Authors and Affiliations
- Laboratory of Epithelial Transport and Pulmonary Division, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa, 52242, USA
Ming Li, John D. McCann & Michael J. Welsh - Cystic Fibrosis Center, Department of Pediatrics, Developmental Genetics and Anatomy, School of Medicine, Case Western Reserve, Cleveland, Ohio, 44106, USA
Carole M. Liedtket - Laboratory of Molecular and Cellular Neuroscience, Rockefeller University, New York, New York, 10021, USA
Angus C. Nairn & Paul Greengard
Authors
- Ming Li
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Li, M., McCann, J., Liedtket, C. et al. Cyclic AMP-dependent protein kinase opens chloride channels in normal but not cystic fibrosis airway epithelium.Nature 331, 358–360 (1988). https://doi.org/10.1038/331358a0
- Received: 19 October 1987
- Accepted: 07 December 1987
- Issue Date: 28 January 1988
- DOI: https://doi.org/10.1038/331358a0