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电荷扫描显示，γ-氨基丁酸（GABA）受体孔道细胞内端存在一个可影响离子选择性的延伸区域。

Charge scan reveals an extended region at the intracellular end of the GABA receptor pore that can influence ion selectivity.

作者信息

Wotring Virginia E, Weiss David S

机构信息

Department of Neurobiology, University of Alabama at Birmingham, AL 35294, USA.

出版信息

J Gen Physiol. 2008 Jan;131(1):87-97. doi: 10.1085/jgp.200609701. Epub 2007 Dec 17.

DOI:10.1085/jgp.200609701
PMID:18079559
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2174155/
Abstract

Selective permeability is a fundamental property of ion channels. The Cys-loop receptor superfamily is composed of both excitatory (ACh, 5-HT) and inhibitory (GABA, glycine) neurotransmitter-operated ion channels. In the GABA receptor, it has been previously shown that the charge selectivity of the integral pore can be altered by a single mutation near the intracellular end of the second transmembrane-spanning domain (TM2). We have extended these findings and now show that charge selectivity of the anionic rho1 GABA receptor can be influenced by the introduction of glutamates, one at a time, over an 8-amino acid stretch (-2' to 5') in the proposed intracellular end of TM2 and the TM1-TM2 intracellular linker. Depending on the position, glutamate substitutions in this region produced sodium to chloride permeability ratios (P(Na)+(/Cl)-) varying from 0.64 to 3.4 (wild type P(Na)+(/Cl)- = 0). In addition to providing insight into the mechanism of ion selectivity, this functional evidence supports a model proposed for the homologous nicotinic acetylcholine receptor in which regions of the protein, in addition to TM2, form the ion pathway.

摘要

选择性通透是离子通道的一项基本特性。半胱氨酸环受体超家族由兴奋性（乙酰胆碱、5-羟色胺）和抑制性（γ-氨基丁酸、甘氨酸）神经递质操纵的离子通道组成。在γ-氨基丁酸受体中，先前的研究表明，第二跨膜结构域（TM2）胞内端附近的单个突变可改变整体孔道的电荷选择性。我们拓展了这些发现，现在表明，在TM2假定的胞内端和TM1-TM2胞内连接子中，一次引入一个谷氨酸，跨越8个氨基酸的片段（-2'至5'），可影响阴离子型rho1γ-氨基丁酸受体的电荷选择性。根据位置不同，该区域的谷氨酸替代产生的钠氯通透率比值（P(Na)+(/Cl)-）在0.64至3.4之间变化（野生型P(Na)+(/Cl)- = 0）。除了有助于深入了解离子选择性机制外，这一功能证据还支持了为同源烟碱型乙酰胆碱受体提出的一个模型，即除TM2外，蛋白质的其他区域也构成离子通道。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c865/2174155/a7b07e93b59d/jgp1310087f07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c865/2174155/13101b10e86a/jgp1310087f01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c865/2174155/0e58b399e1ee/jgp1310087f02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c865/2174155/e102cc293a44/jgp1310087f03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c865/2174155/6dcf8781e308/jgp1310087f04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c865/2174155/27c08a628d1a/jgp1310087f05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c865/2174155/2285f5fabbf0/jgp1310087f06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c865/2174155/a7b07e93b59d/jgp1310087f07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c865/2174155/13101b10e86a/jgp1310087f01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c865/2174155/0e58b399e1ee/jgp1310087f02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c865/2174155/e102cc293a44/jgp1310087f03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c865/2174155/6dcf8781e308/jgp1310087f04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c865/2174155/27c08a628d1a/jgp1310087f05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c865/2174155/2285f5fabbf0/jgp1310087f06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c865/2174155/a7b07e93b59d/jgp1310087f07.jpg

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