Referenced in: none

Automatically associated channels: ClC2 , ClC4

Title: Inhibition of CLC-2 chloride channel expression interrupts expansion of fetal lung cysts.

Authors: Carol J Blaisdell, Marcelo M Morales, Ana Carolina Oliveira Andrade, Penelope Bamford, Michael Wasicko, Paul Welling

Journal, date & volume: Am. J. Physiol. Lung Cell Mol. Physiol., 2004 Feb , 286, L420-6

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/14711803

Abstract
Normal lung morphogenesis is dependent on chloride-driven fluid transport. The molecular identity of essential fetal lung chloride channel(s) has not been elucidated. CLC-2 is a chloride channel, which is expressed on the apical surface of the developing respiratory epithelium. CLC-2-like pH-dependent chloride secretion exists in fetal airway cells. We used a 14-day fetal rat lung submersion culture model to examine the role of CLC-2 in lung development. In this model, the excised fetal lung continues to grow, secrete fluid, and become progressively cystic in morphology (26). We inhibited CLC-2 expression in these explants, using antisense oligonucleotides, and found that lung cyst morphology was disrupted. In addition, transepithelial voltage (V(t)) of lung explants transfected with antisense CLC-2 was inhibited with V(t) = -1.5 +/- 0.2 mV (means + SE) compared with -3.7 +/- 0.3 mV (means + SE) for mock-transfected controls and -3.3 +/- 0.3 mV (means + SE) for nonsense oligodeoxynucleotide-transfected controls. This suggests that CLC-2 is important for fetal lung fluid production and that it may play a role in normal lung morphogenesis.