The heterotrimeric g protein gi-2 inhibits outwardly rectifying
chloride channels in human airway epithelial cells.
Schwiebert, Erik M., Dieter C. Gruenert, William B. Guggino, and Bruce
A. Stanton.
Department of Physiology, Dartmouth Medical School, Hanover, NH,
Cardiovascular Research Institute, University of California at San
Francisco, San Francisco, CA, Departments of Physiology and
Pediatrics, Johns Hopkins University School of Medicine, Baltimore,
MD
APStracts 2:0125C, 1995.
Previously we demonstrated that the heterotrimeric G protein, Gi-2,
inhibits cystic fibrosis transmembrane conductance regulator (CFTR)
chloride (Cl-) channels in human airway epithelial cells {21,23}. The
goal of the present study was to determine if G proteins also
regulate outwardly rectifying Cl- channels (ORCCs), a distinct class
of Cl- channels regulated defectively by PKA in cystic fibrosis (CF).
To this end, we used the patch-clamp technique to study ORCCs in a
normal human airway epithelial cell line (9HTEo-) which expresses
CFTR and ORCCs. Stimulation of G proteins with GTP and GTPS decreased
the single channel open probability (Po) of ORCCs, whereas inhibition
of G proteins by GDPS increased the Po. Moreover, pertussis toxin
(PTX), an uncoupler of Gi and Go subclasses of heterotrimeric G
proteins, also increased the Po. Purified Gi-2 decreased the Po. In
contrast, other PTX-sensitive G proteins, Gi-1, Gi-3 and Go, had no
effect on Po. We propose that Gi-2 couples to a receptor whose
agonist negatively regulates ORCCs in human airway epithelial cells.
Received 30 November 1994; accepted in final form 13 January
1995.
APS Manuscript Number C700-4.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 10 March 1995.