NDLI: 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.

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

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Welsh, M. J. Anderson, M. P.
Description	Author Affiliation: Anderson MP ( Howard Hughes Medical Institute, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242.);
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.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	14
Volume Number	88
Language	English
Publisher	National Academy of Sciences
Publisher Date	1991-08-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Calcium Pharmacology Cyclic AMP Cystic Fibrosis Physiopathology Ion Channels Physiology Membrane Proteins Cell Line Cell Membrane Cells, Cultured Chloride Channels Epithelium Intestines Ionomycin Kinetics Membrane Potentials Drug Effects Models, Biological Reference Values Respiratory Physiological Phenomena Respiratory System Comparative Study Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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