Calcium and cAMP activate different chloride channels in the apical membrane of normal and cystic fibrosis epithelia

Matthew P Anderson; Michael J. Welsh

doi:10.1073/pnas.88.14.6003

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Calcium and cAMP activate different chloride channels in the apical membrane of normal and cystic fibrosis epithelia

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Calcium and cAMP activate different chloride channels in the apical membrane of normal and cystic fibrosis epithelia

Matthew P Anderson and Michael J. Welsh

Proceedings of the National Academy of Sciences - PNAS, Vol.88(14), pp.6003-6007

07/15/1991

DOI: 10.1073/pnas.88.14.6003

PMCID: PMC52010

PMID: 1712478

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Abstract

The genetic disease cystic fibrosis (CF) causes decreased Cl- transport in several epithelia. cAMP-dependent regulation of apical membrane Cl- channels is defective in CF airway epithelia; as a result, CF epithelia fail to secrete Cl-. In contrast, Ca(2+)-stimulated Cl- secretion is intact in CF airway epithelia and thus has the potential to bypass the CF Cl- secretory defect. For a Cl- channel to govern Cl- secretion, it must be located in the apical membrane. To specifically investigate apical membrane Cl- channels, we studied cells grown on permeable filter supports and measured Cl- currents across the apical membrane. We found that Ca2+ and cAMP activate different Cl- channels in the apical membrane. (i) Ca(2+)-activated Cl- channels were present in the apical membrane of airway but not in intestinal epithelia. (ii) cAMP- but not Ca(2+)-activated Cl- channels were defective in CF airway epithelia. (iii) Ca(2+)- but not cAMP-activated Cl- channels were blocked by 4,4'-diisothiocyanato-2,2'-stilbenedisulfonate. (iv) Ca(2+)- and cAMP-activated apical channels had different anion permeabilities. (v) An increase in both second messengers produced an additive increase in Cl- current. These results also explain the puzzling observation that Ca(2+)-stimulated Cl- secretion is defective in CF intestine: the Ca(2+)-activated Cl- channels that could circumvent the Cl- secretory defect in CF airway are missing from the apical membrane of intestinal epithelia.

Details

Title: Subtitle: Calcium and cAMP activate different chloride channels in the apical membrane of normal and cystic fibrosis epithelia
Creators: Matthew P Anderson - Howard Hughes Medical Institute, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242
Michael J. Welsh - Howard Hughes Medical Institute, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242
Resource Type: Journal article
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.88(14), pp.6003-6007
DOI: 10.1073/pnas.88.14.6003
PMID: 1712478
PMCID: PMC52010
NLM abbreviation: Proc Natl Acad Sci U S A
ISSN: 0027-8424
eISSN: 1091-6490
Publisher: National Academy of Sciences
Language: English
Date published: 07/15/1991
Academic Unit: Neurology; Molecular Physiology and Biophysics; Neurosurgery; Internal Medicine
Record Identifier: 9984020703602771

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