Human cystic fibrosis airway epithelia have reduced Clâˆ’ conductance but not increased Na+ conductance

Omar A Itani; Jeng-Haur Chen; Philip H Karp; Sarah Ernst; Shaf Keshavjee; Kalpaj Parekh; Julia Klesney-Tait; Joseph Zabner; Michael J Welsh

doi:10.1073/pnas.1106695108

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Human cystic fibrosis airway epithelia have reduced Clâˆ’ conductance but not increased Na+ conductance

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Human cystic fibrosis airway epithelia have reduced Clâˆ’ conductance but not increased Na+ conductance

Omar A Itani, Jeng-Haur Chen, Philip H Karp, Sarah Ernst, Shaf Keshavjee, Kalpaj Parekh, Julia Klesney-Tait, Joseph Zabner and Michael J Welsh

Proceedings of the National Academy of Sciences - PNAS, Vol.108(25), pp.10260-10265

06/21/2011

DOI: 10.1073/pnas.1106695108

PMCID: PMC3121869

PMID: 21646513

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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 CFTR ΔF508/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.

epithelial Na+ channels

Biological Sciences

chloride secretion

Details

Title: Subtitle: Human cystic fibrosis airway epithelia have reduced Clâˆ’ conductance but not increased Na+ conductance
Creators: Omar A Itani - Departments of
Jeng-Haur Chen - Departments of
Philip H Karp - Departments of
Sarah Ernst - Departments of
Shaf Keshavjee - Toronto Lung Transplant Program
Kalpaj Parekh - Cardiothoracic Surgery, and
Julia Klesney-Tait - Departments of
Joseph Zabner - Departments of
Michael J Welsh - Departments of
Resource Type: Journal article
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.108(25), pp.10260-10265
DOI: 10.1073/pnas.1106695108
PMID: 21646513
PMCID: PMC3121869
NLM abbreviation: Proc Natl Acad Sci U S A
ISSN: 0027-8424
eISSN: 1091-6490
Publisher: National Academy of Sciences
Language: English
Date published: 06/21/2011
Academic Unit: Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Anatomy and Cell Biology; Surgery; Cardiothoracic Surgery; Neurosurgery; Internal Medicine
Record Identifier: 9984013116502771

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