Journal article
Bioelectric Properties of Chloride Channels in Human, Pig, Ferret, and Mouse Airway Epithelia
American journal of respiratory cell and molecular biology, Vol.36(3), pp.313-323
03/2007
DOI: 10.1165/rcmb.2006-0286OC
PMCID: PMC1894945
PMID: 17008635
Abstract
The development of effective therapies for cystic fibrosis (CF) requires animal models that can appropriately reproduce the human disease phenotype. CF mouse models have demonstrated cAMP-inducible, non–CF transmembrane conductance regulator (non-CFTR) chloride transport in conducting airway epithelia, and this property is thought to be responsible for the lack of a spontaneous CF-like phenotype in the lung. Thus, an understanding of species diversity in airway epithelial electrolyte transport and CFTR function is critical to developing better models for CF. Two species currently being used in attempts to develop better animal models of CF include the pig and ferret. In the study reported here, we sought to comparatively characterize the bioelectric properties of
in vitro
polarized airway epithelia—from human, mouse, pig and ferret—grown at the air–liquid interface (ALI). Bioelectric properties analyzed include amiloride-sensitive Na
+
transport, 4,4′-diisothiocyanato-stilbene-2,2′-disulfonic acid (DIDS)-sensitive Cl
−
transport, and cAMP-sensitive Cl
−
transport. In addition, as an index for CFTR functional conservation, we evaluated the ability of four CFTR inhibitors, including glibenclamide, 5-nitro-2-(3-phenylpropyl-amino)-benzoic acid, CFTR
inh
-172, and CFTR
inh
-GlyH101, to block cAMP-mediated Cl
−
transport. Compared with human epithelia, pig epithelia demonstrated enhanced amiloride-sensitive Na
+
transport. In contrast, ferret epithelia exhibited significantly reduced DIDS-sensitive Cl
−
transport. Interestingly, although the four CFTR inhibitors effectively blocked cAMP-mediated Cl
−
secretion in human airway epithelia, each species tested demonstrated unique differences in its responsiveness to these inhibitors. These findings suggest the existence of substantial species-specific differences at the level of the biology of airway epithelial electrolyte transport, and potentially also in terms of CFTR structure/function.
Details
- Title: Subtitle
- Bioelectric Properties of Chloride Channels in Human, Pig, Ferret, and Mouse Airway Epithelia
- Creators
- Xiaoming Liu - Departments of Anatomy and Cell Biology and Internal Medicine, and The Center for Gene Therapy, College of Medicine, The University of Iowa, Iowa City, IowaMeihui Luo - Departments of Anatomy and Cell Biology and Internal Medicine, and The Center for Gene Therapy, College of Medicine, The University of Iowa, Iowa City, IowaLiang Zhang - Departments of Anatomy and Cell Biology and Internal Medicine, and The Center for Gene Therapy, College of Medicine, The University of Iowa, Iowa City, IowaWei Ding - Departments of Anatomy and Cell Biology and Internal Medicine, and The Center for Gene Therapy, College of Medicine, The University of Iowa, Iowa City, IowaZiying Yan - Departments of Anatomy and Cell Biology and Internal Medicine, and The Center for Gene Therapy, College of Medicine, The University of Iowa, Iowa City, IowaJohn F Engelhardt - Departments of Anatomy and Cell Biology and Internal Medicine, and The Center for Gene Therapy, College of Medicine, The University of Iowa, Iowa City, Iowa
- Resource Type
- Journal article
- Publication Details
- American journal of respiratory cell and molecular biology, Vol.36(3), pp.313-323
- DOI
- 10.1165/rcmb.2006-0286OC
- PMID
- 17008635
- PMCID
- PMC1894945
- NLM abbreviation
- Am J Respir Cell Mol Biol
- ISSN
- 1044-1549
- eISSN
- 1535-4989
- Publisher
- American Thoracic Society
- Language
- English
- Date published
- 03/2007
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Anatomy and Cell Biology; Radiation Oncology; Internal Medicine
- Record Identifier
- 9984025473902771
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