Journal article
Defective fluid transport by cystic fibrosis airway epithelia
The Journal of clinical investigation, Vol.93(3), pp.1307-1311
03/1994
DOI: 10.1172/JCI117087
PMCID: PMC294089
PMID: 8132771
Abstract
Cystic fibrosis (CF) airway epithelia exhibit defective transepithelial electrolyte transport: cAMP-stimulated Cl- secretion is abolished because of the loss of apical membrane cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channels, and amiloride-sensitive Na+ absorption is increased two- to threefold because of increased amiloride-sensitive apical Na+ permeability. These abnormalities are thought to alter respiratory tract fluid, thereby contributing to airway disease, the major source of mortality in this genetic disease. However, the underlying hypothesis, that fluid transport is abnormal in CF airway epithelia, has not been tested. Most conjecture about fluid transport is based on measurements of Na+ and Cl- transport performed under short circuit conditions in Ussing chambers. But such studies differ from in vivo conditions in that transepithelial voltage and mucosal fluid composition are held constant. Therefore, we measured fluid transport and mucosal electrolyte composition in primary cultures of CF airway epithelia without holding transepithelial voltage and ion concentration gradients at zero. In normal epithelia, cAMP agonists plus amiloride stimulated NaCl and fluid secretion. In CF epithelia, cAMP agonists failed to stimulate fluid or electrolyte secretion, changes consistent with the loss of CFTR Cl- channels. But in striking contrast to predictions based on Ussing chamber studies, CF epithelia absorbed fluid at a rate no greater than normal epithelia. Moreover, amiloride, which inhibits Na+ channels, failed to inhibit fluid absorption by CF epithelia. These results have important implications for understanding the pathogenesis of CF airway disease and for the design and evaluation of therapy.
Details
- Title: Subtitle
- Defective fluid transport by cystic fibrosis airway epithelia
- Creators
- J J Smith - Department of Pediatrics, University of Iowa College of Medicine, Iowa City 52242P H Karp - Department of Pediatrics, University of Iowa College of Medicine, Iowa City 52242M J Welsh - Department of Pediatrics, University of Iowa College of Medicine, Iowa City 52242
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.93(3), pp.1307-1311
- DOI
- 10.1172/JCI117087
- PMID
- 8132771
- PMCID
- PMC294089
- ISSN
- 0021-9738
- eISSN
- 1558-8238
- Language
- English
- Date published
- 03/1994
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Stead Family Department of Pediatrics; Fraternal Order of Eagles Diabetes Research Center; Neurosurgery; Internal Medicine
- Record Identifier
- 9984013915902771
Metrics
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