G protein Gα(i-2) inhibits outwardly rectifying chloride channels in human airway epithelial cells

E. M. Schwiebert, D. C. Gruenert, William B Guggino, B. A. Stanton

Research output: Contribution to journalArticle

Abstract

Previously we demonstrated that the heterotrimeric G protein, Gα(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 GTPγS decreased the single- channel open probability (P(o)) of ORCC, whereas inhibition of G proteins by GDPβS increased the P(o). Moreover, pertussis toxin (PTX), an uncoupler of G(i) and G(o) subclasses of heterotrimeric G proteins, also increased the P(o). Purified Gα(i-2) decreased the P(o). In contrast, other PTX-sensitive G proteins, Gα(i-1), Gα(i-3), and Gα(o), had no effect on P(o). We propose that Gα(i-2) couples to a receptor whose agonist negatively regulates ORCC in human airway epithelial cells.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume269
Issue number2 38-2
StatePublished - 1995

Fingerprint

chloride channels
Chloride Channels
G-proteins
GTP-Binding Proteins
epithelial cells
Epithelial Cells
cystic fibrosis
Heterotrimeric GTP-Binding Proteins
Cystic Fibrosis Transmembrane Conductance Regulator
Pertussis Toxin
pertussis toxin
Clamping devices
Patch-Clamp Techniques
patch-clamp technique
Cyclic AMP-Dependent Protein Kinases
Guanosine Triphosphate
cAMP-dependent protein kinase
Cystic Fibrosis
agonists
Cell Line

Keywords

  • cystic fibrosis
  • patch clamp

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology
  • Agricultural and Biological Sciences(all)

Cite this

G protein Gα(i-2) inhibits outwardly rectifying chloride channels in human airway epithelial cells. / Schwiebert, E. M.; Gruenert, D. C.; Guggino, William B; Stanton, B. A.

In: American Journal of Physiology - Cell Physiology, Vol. 269, No. 2 38-2, 1995.

Research output: Contribution to journalArticle

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