Human cystic fibrosis airway epithelia have reduced Cl − conductance but not increased Na + conductance
Open Access
- 6 June 2011
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 108 (25), 10260-10265
- https://doi.org/10.1073/pnas.1106695108
Abstract
Loss of cystic fibrosis transmembrane conductance regulator (CFTR) anion channel function causes cystic fibrosis (CF) lung disease. CFTR is expressed in airway epithelia, but how CF alters electrolyte transport across airway epithelia has remained uncertain. Recent studies of a porcine model showed that in vivo, excised, and cultured CFTR−/− and CFTRΔF508/ΔF508 airway epithelia lacked anion conductance, and they did not hyperabsorb Na+. Therefore, we asked whether Cl− and Na+ conductances were altered in human CF airway epithelia. We studied differentiated primary cultures of tracheal/bronchial epithelia and found that transepithelial conductance (Gt) under basal conditions and the cAMP-stimulated increase in Gt were markedly attenuated in CF epithelia compared with non-CF epithelia. These data reflect loss of the CFTR anion conductance. In CF and non-CF epithelia, the Na+ channel inhibitor amiloride produced similar reductions in Gt and Na+ absorption, indicating that Na+ conductance in CF epithelia did not exceed that in non-CF epithelia. Consistent with previous reports, adding amiloride caused greater reductions in transepithelial voltage and short-circuit current in CF epithelia than in non-CF epithelia; these changes are attributed to loss of a Cl− conductance. These results indicate that Na+ conductance was not increased in these cultured CF tracheal/bronchial epithelia and point to loss of anion transport as key to airway epithelial dysfunction in CF.Keywords
This publication has 51 references indexed in Scilit:
- Hyperviscous airway periciliary and mucous liquid layers in cystic fibrosis measured by confocal fluorescence photobleachingThe FASEB Journal, 2011
- The Δ F508 Mutation Causes CFTR Misprocessing and Cystic Fibrosis–Like Disease in PigsScience Translational Medicine, 2011
- Acute Regulation of the Epithelial Sodium Channel in Airway Epithelia by Proteases and TraffickingAmerican Journal of Respiratory Cell and Molecular Biology, 2010
- Role of epithelial HCO3−transport in mucin secretion: lessons from cystic fibrosisAmerican Journal of Physiology-Cell Physiology, 2010
- Loss of Anion Transport without Increased Sodium Absorption Characterizes Newborn Porcine Cystic Fibrosis Airway EpitheliaCell, 2010
- Disease phenotype of a ferret CFTR-knockout model of cystic fibrosisJCI Insight, 2010
- Cystic Fibrosis Pigs Develop Lung Disease and Exhibit Defective Bacterial Eradication at BirthScience Translational Medicine, 2010
- Rescue of CF airway epithelial cell function in vitro by a CFTR potentiator, VX-770Proceedings of the National Academy of Sciences, 2009
- Disruption of the CFTR Gene Produces a Model of Cystic Fibrosis in Newborn PigsScience, 2008
- Thiazolidinone CFTR inhibitor identified by high-throughput screening blocks cholera toxin–induced intestinal fluid secretionJCI Insight, 2002