Gαi controls the gating of the G protein-activated K+ channel, GIRK

被引:137
作者
Peleg, S
Varon, D
Ivanina, T
Dessauer, CW
Dascal, N [1 ]
机构
[1] Tel Aviv Univ, Sackler Sch Med, Dept Physiol & Pharmacol, IL-69978 Tel Aviv, Israel
[2] Univ Texas, Houston Med Sch, Dept Integrat Biol & Pharmacol, Houston, TX 77030 USA
关键词
D O I
10.1016/S0896-6273(01)00567-0
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
GIRK (Kir3) channels are activated by neurotransmitters; coupled to G proteins, via a direct binding of Gbetagamma. The role of Galpha subunits in GIRK gating is elusive. Here we demonstrate that Galpha(i) is not only a donor of Gbetagamma but also regulates GIRK gating. When overexpressed in Xenopus oocytes, GIRK channels show excessive basal activity and poor activation by agonist or Gbetagamma. Coexpression of Galpha(i3) or Galpha(i1), restores the correct gating parameters. Galpha(i) acts neither as a pure Gbetagamma scavenger nor as an allosteric cofactor for Gbetagamma. It inhibits only the basal activity without interfering with Gbetagamma-induced response. Thus, GIRK is regulated, in distinct ways, by both arms of the G protein. Gal probably acts in its GDP bound form, alone or as a part of Galphabetagamma heterotrimer.
引用
收藏
页码:87 / 99
页数:13
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