G-PROTEIN G-ALPHA(I-2) INHIBITS OUTWARDLY RECTIFYING CHLORIDE CHANNELS IN HUMAN AIRWAY EPITHELIAL-CELLS

被引:16
作者
SCHWIEBERT, EM
GRUENERT, DC
GUGGINO, WB
STANTON, BA
机构
[1] JOHNS HOPKINS UNIV, SCH MED, DEPT PEDIAT, BALTIMORE, MD 21205 USA
[2] DARTMOUTH COLL, SCH MED, DEPT PHYSIOL, HANOVER, NH 03755 USA
[3] UNIV CALIF SAN FRANCISCO, DEPT LAB MED, CARDIOVASC RES INST, SAN FRANCISCO, CA 94143 USA
[4] UNIV CALIF SAN FRANCISCO, CTR GENE THERAPY CARE, SAN FRANCISCO, CA 94143 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY | 1995年 / 269卷 / 02期
关键词
CYSTIC FIBROSIS; PATCH CLAMP;
D O I
10.1152/ajpcell.1995.269.2.C451
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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 (P-o) of ORCC, whereas inhibition of G proteins by GDP beta S 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 G alpha(i-2) decreased the P-o. In contrast, other PTX-sensitive G proteins, G alpha(i-1), G alpha(i-3), and G alpha(o), had no effect on P-o. We propose that G alpha(i-2) couples to a receptor whose agonist negatively regulates ORCC in human airway epithelial cells.
引用
收藏
页码:C451 / C456
页数:6
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