G protein G alpha i-2 inhibits outwardly rectifying chloride channels in human airway epithelial cells.
G protein G alpha i-2 inhibits outwardly rectifying chloride channels in human airway epithelial cells.
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G 蛋白 G α i-2 抑制人气道上皮细胞中的向外整流氯离子通道。
DOI：
10.1152/ajpcell.1995.269.2.c451
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Stanton,BA
中科院分区：
文献类型：
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作者：
Schwiebert,EM;Gruenert,DC;Guggino,WB;Stanton,BA
先前我们证明了异源三聚体G蛋白G α i-2抑制人气道上皮细胞中囊性纤维化跨膜传导调节因子（CFTR）氯离子（Cl-）通道（E. M. Schwiebert，F.格塞克湖埃尔科拉尼角Wjasow，D. C. Gruenert和B。A.斯坦顿Am. J.Physiol.267（Cell Physiol.36）：C272-C281，1994和E. M. Schwiebert，N. L. Kizer，D. C. Gruenert和B。A.斯坦顿Proc. Natl. Acad. Sci. USA 89：10623-10627，1992）。本研究的目的是确定G蛋白是否也调节外向整流性Cl-通道（ORCC），这是囊性纤维化（CF）中由蛋白激酶A（PKA）缺陷调节的一类独特的Cl-通道。为此，我们使用膜片钳技术研究了正常人气道上皮细胞系（9 HTEo-）中表达CFTR和ORCC的ORCC。用GTP和GTP γ S刺激G蛋白降低ORCC的单通道开放概率（Po），而GDP β S抑制G蛋白增加Po。此外，百日咳毒素（PTX），解偶联剂的Gi和G（o）亚类的异源三聚体G蛋白，也增加了Po。纯化的G α i-2降低了Po.相比之下，其他PTX敏感性G蛋白G α i-1、G α i-3和G α o对Po没有影响。我们提出G α i-2与受体偶联，其激动剂负调节人气道上皮细胞中的ORCC。
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.