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

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

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


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 (Vt) 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.

Original languageEnglish (US)
Pages (from-to)L420-L426
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Issue number2 30-2
StatePublished - Feb 2004
Externally publishedYes


  • Chloride secretion
  • Lung development

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology


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