title: ClC-5: ontogeny of an alternative chloride channel in respiratory epithelia.
abstract: Chloride transport is critical to many functions of the lung. Molecular defects in the best-known chloride channel, cystic fibrosis transmembrane conductance regulator (CFTR), lead to impaired function of airway defensins, hydration of airway surface fluid, and mucociliary clearance leading to chronic lung disease, and premature death, but do not cause defects in lung development. We examined the expression of one member of the ClC family of volume- and voltage-regulated channels using the ribonuclease protection assay and Western blot analysis in rats. ClC-5 mRNA and protein are most strongly expressed in the fetal lung, and expression is maintained although downregulated postnatally. In addition, using immunocytochemistry, we find that ClC-5 is predominantly expressed along the luminal surface of the airway epithelium, suggesting that ClC-5 may participate in lung chloride secretion. Identifying candidate genes for critical ion transport functions is essential for understanding normal lung morphogenesis and the pathophysiology of several lung diseases. In addition, the manipulation of non-CFTR chloride channels may provide a viable approach for treating cystic fibrosis lung disease.
authors.affiliation: Department of Pediatrics, Eudowood Division of Respiratory Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Rebecca D
authors.initials: RD
authors.lastname: Edmonds
authors.forename: Ian V
authors.initials: IV
authors.lastname: Silva
authors.forename: William B
authors.initials: WB
authors.lastname: Guggino
authors.forename: Robert B
authors.initials: RB
authors.lastname: Butler
authors.forename: Pamela L
authors.initials: PL
authors.lastname: Zeitlin
authors.forename: Carol J
authors.initials: CJ
authors.lastname: Blaisdell
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000378:metabolism*; D018118:Chloride Channels / Q000235:genetics / Q000378:metabolism*; D005314:Embryonic and Fetal Development; D004848:Epithelium / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D005333:Fetus / Q000378:metabolism; D008168:Lung / Q000196:embryology* / Q000254:growth & development* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D014132:Trachea / Q000196:embryology* / Q000254:growth & development* / Q000378:metabolism
chemical_list: D018118:Chloride Channels; D012333:RNA, Messenger