EXP-1 is an excitatory GABA-gated cation channel
EXP-1 is an excitatory GABA-gated cation channel
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DOI：
10.1038/nn1136
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发表时间：
2003-11-01
影响因子：
25
通讯作者：
Jorgensen, EM
中科院分区：
文献类型：
--
作者：
Beg, AA;Jorgensen, EM
γ-氨基丁酸（GABA）通过激活阴离子选择性配体门控离子通道介导快速抑制性神经传递。虽然电生理学研究表明，GABA可以激活阳离子选择性配体门控离子通道在某些类型的细胞，这样的通道从来没有在分子水平上的特点。在这里，我们表明，GABA介导肠肌收缩线虫线虫通过EXP-1受体，阳离子选择性配体门控离子通道。EXP-1蛋白在几乎所有结构域中与离子型GABA受体亚基相似。然而，在EXP-1的成孔结构域中，赋予阴离子选择性的残基被交换为指定阳离子选择性的残基。当在非洲爪蟾卵母细胞中表达时，EXP-1形成可渗透阳离子而非阴离子的GABA受体。我们的结论是，一些分配给GABA的兴奋功能是由阳离子通道，而不是由阴离子通道介导的。
gamma-aminobutyric acid (GABA) mediates fast inhibitory neurotransmission by activating anion-selective ligand-gated ion channels. Although electrophysiological studies indicate that GABA may activate cation-selective ligand-gated ion channels in some cell types, such a channel has never been characterized at the molecular level. Here we show that GABA mediates enteric muscle contraction in the nematode Caenorhabditis elegans via the EXP-1 receptor, a cation-selective ligand-gated ion channel. The EXP-1 protein resembles ionotropic GABA receptor subunits in almost all domains. In the pore-forming domain of EXP-1, however, the residues that confer anion selectivity are exchanged for those that specify cation selectivity. When expressed in Xenopus laevis oocytes, EXP-1 forms a GABA receptor that is permeable to cations and not anions. We conclude that some of the excitatory functions assigned to GABA are mediated by cation channels rather than by anion channels.