G-protein-coupled inwardly rectifying potassium channels are targets of alcohol action
G-protein-coupled inwardly rectifying potassium channels are targets of alcohol action
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DOI：
10.1038/16012
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发表时间：
1999-12-01
影响因子：
25
通讯作者：
Harris, RA
中科院分区：
文献类型：
--
作者：
Lewohl, JM;Wilson, WR;Harris, RA
G蛋白偶联的内向整流钾通道（GIRKs）对调节突触传递和神经元放电频率非常重要。由于它们在脑功能中起关键作用，我们探究这些钾通道是否为酒精作用的靶点。乙醇增强了与γ - 氨基丁酸B型（GABA(B)）受体偶联的小脑颗粒细胞GIRKs的功能。利用表达同源或异源通道的非洲爪蟾卵母细胞详细研究了乙醇对GIRK功能的增强作用。所有GIRK通道的功能都被致醉浓度的乙醇增强，但其他相关的内向整流钾通道未受影响。通过GIRK2/IRK1嵌合体和GIRK2截短突变体确定了羧基（C）末端的一个由43个氨基酸组成的区域，该区域对乙醇在这些通道上的作用至关重要。
C-protein-coupled inwardly rectifying potassium channels (GIRKs) are important for regulation of synaptic transmission and neuronal firing rates. Because of their key role in brain function, we asked if these potassium channels are targets of alcohol action. Ethanol enhanced function of cerebellar granule cell GIRKs coupled to GABA(B) receptors. Enhancement of GIRK function by ethanol was studied in detail using Xenopus oocytes expressing homomeric or heteromeric channels. Function of all GIRK channels was enhanced by intoxicating concentrations of ethanol, but other, related inwardly rectifying potassium channels were not affected. GIRK2/IRK1 chimeras and GIRK2 truncation mutants were used to identify a region of 43 amino acids in the carboxyl (C) terminus that is critical for the action of ethanol on these channels.