Bioelectric properties of chloride channels in human, pig, ferret, and mouse airway epithelia

Am J Respir Cell Mol Biol. 2007 Mar;36(3):313-23. doi: 10.1165/rcmb.2006-0286OC. Epub 2006 Sep 28.


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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Differentiation / drug effects
  • Cell Polarity / drug effects
  • Cells, Cultured
  • Chloride Channels / antagonists & inhibitors
  • Chloride Channels / metabolism*
  • Cyclic AMP / metabolism
  • Cystic Fibrosis Transmembrane Conductance Regulator / antagonists & inhibitors
  • Cystic Fibrosis Transmembrane Conductance Regulator / chemistry
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics
  • Cystic Fibrosis Transmembrane Conductance Regulator / metabolism
  • Electric Conductivity*
  • Epithelial Cells / cytology
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Epithelium / drug effects
  • Epithelium / metabolism*
  • Epithelium / ultrastructure
  • Ferrets / metabolism*
  • Gene Expression Regulation / drug effects
  • Humans
  • Ion Channel Gating / drug effects
  • Membrane Transport Modulators / pharmacology
  • Mice
  • Molecular Sequence Data
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Species Specificity
  • Swine / metabolism*
  • Tissue Culture Techniques
  • Trachea* / cytology


  • Chloride Channels
  • Membrane Transport Modulators
  • RNA, Messenger
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Cyclic AMP