G protein G alpha i-2 inhibits outwardly rectifying chloride channels in human airway epithelial cells

Am J Physiol. 1995 Aug;269(2 Pt 1):C451-6. doi: 10.1152/ajpcell.1995.269.2.C451.


Previously we demonstrated that the heterotrimeric G protein, G alpha i-2, inhibits cystic fibrosis transmembrane conductance regulator (CFTR) chloride (Cl-) channels in human airway epithelial cells (E. M. Schwiebert, F. Gesek, L. Ercolani, C. Wjasow, D. C. Gruenert, and B. A. Stanton. Am. J. Physiol. 267 (Cell Physiol. 36): C272-C281, 1994, and E. M. Schwiebert, N. L. Kizer, D. C. Gruenert, and B. A. Stanton. Proc. Natl. Acad. Sci. USA 89: 10623-10627, 1992). The goal of the present study was to determine if G proteins also regulate outwardly rectifying Cl- channels (ORCC), a distinct class of Cl- channels regulated defectively by protein kinase A (PKA) in cystic fibrosis (CF). To this end, we used the patch-clamp technique to study ORCC in a normal human airway epithelial cell line (9HTEo-) that expresses CFTR and ORCC. Stimulation of G proteins with GTP and GTP gamma S decreased the single-channel open probability (Po) of ORCC, whereas inhibition of G proteins by GDP beta S increased the Po. Moreover, pertussis toxin (PTX), an uncoupler of Gi and G(o) subclasses of heterotrimeric G proteins, also increased the Po. Purified G alpha i-2 decreased the Po. In contrast, other PTX-sensitive G proteins, G alpha i-1, G alpha i-3, and G alpha o, had no effect on Po. We propose that G alpha i-2 couples to a receptor whose agonist negatively regulates ORCC in human airway epithelial cells.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Triphosphate / pharmacology
  • Catalysis
  • Cell Line
  • Chloride Channels / antagonists & inhibitors*
  • Chloride Channels / drug effects
  • Chloride Channels / metabolism
  • Cyclic AMP-Dependent Protein Kinases / pharmacology
  • Cystic Fibrosis / metabolism
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Epithelial Cells
  • Epithelium / metabolism
  • GTP-Binding Proteins / physiology*
  • Humans
  • Membrane Proteins / metabolism
  • Patch-Clamp Techniques
  • Pertussis Toxin
  • Trachea / cytology
  • Trachea / metabolism*
  • Virulence Factors, Bordetella / pharmacology


  • CFTR protein, human
  • Chloride Channels
  • Membrane Proteins
  • Virulence Factors, Bordetella
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Adenosine Triphosphate
  • Pertussis Toxin
  • Cyclic AMP-Dependent Protein Kinases
  • GTP-Binding Proteins