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A Nonproton Ligand Sensor in the Acid-Sensing Ion Channel
文献类型：期刊论文
| 作者 | Yu, Ye ; Chen, Zhi ; Li, Wei-Guang ; Cao, Hui ; Feng, En-Guang ; Yu, Fang ; Liu, Hong ; Jiang, Hualiang ; Xu, Tian-Le(徐天乐) |
| 刊名 | NEURON
 |
| 出版日期 | 2010 |
| 卷号 | 68期号:1页码:61-72 |
| ISSN号 | 0896-6273 |
| 关键词 | TARANTULA TOXIN PSALMOTOXIN-1 DORSAL-HORN NEURONS TRP CHANNELS MECHANOSENSORY FUNCTION EXTRACELLULAR DOMAIN INFLAMMATORY PAIN ASIC 1A MODULATION ISCHEMIA CA2+ |
| 通讯作者 | Jiang, HL (reprint author), Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China,hljiang@mail.shcnc.ac.cn |
| 英文摘要 | Acid-sensing ion channels (ASICs) have long been considered as extracellular proton (H(+))-gated cation channels, and peripheral ASIC3 channels seem to be a natural sensor of acidic pain. Here, we report the identification of a nonproton sensor on ASIC3. We show first that 2-guanidine-4-methylquinazoline (GMQ) causes persistent ASIC3 channel activation at the normal pH. Using GMQ as a probe and combining mutagenesis and covalent modification analysis, we then uncovered a ligand sensor lined by residues around E423 and E79 of the extracellular "palm" domain of the ASIC3 channel that-is crucial for activation by nonproton activators. Furthermore, we show that GMQ activates sensory neurons and causes pain-related behaviors in an ASIC3,dependent manner, indicating the functional significance of ASIC activation by nonproton ligands. Thus, natural ligands beyond protons may activate ASICs under physiological and pathological conditions through the nonproton ligand sensor, serving for channel activation independent of abrupt and marked acidosis. |
| 学科主题 | Neurosciences & Neurology |
| 资助信息 | National Natural Science Foundation of China[30830035, 30700145, 9091300]; National Basic Research Program of China[2006CB500803, 2011CB809005, 2009CB918502]; Shanghai Municipal Government[09XD1404900]; K.C. Wong Education Foundation (Hong Kong); China Postdoctoral Science Foundation |
| 收录类别 | SCI |
| 语种 | 英语 |
| 公开日期 | 2012-07-13 |
| 源URL | [http://ir.sibs.ac.cn/handle/331001/1568]  |
| 专题 | 上海神经科学研究所_神经所(总) |
| 推荐引用方式 GB/T 7714 | Yu, Ye,Chen, Zhi,Li, Wei-Guang,et al. A Nonproton Ligand Sensor in the Acid-Sensing Ion Channel[J]. NEURON,2010,68(1):61-72. |
| APA | Yu, Ye.,Chen, Zhi.,Li, Wei-Guang.,Cao, Hui.,Feng, En-Guang.,...&Xu, Tian-Le.(2010).A Nonproton Ligand Sensor in the Acid-Sensing Ion Channel.NEURON,68(1),61-72. |
| MLA | Yu, Ye,et al."A Nonproton Ligand Sensor in the Acid-Sensing Ion Channel".NEURON 68.1(2010):61-72. |
入库方式： OAI收割
来源：上海神经科学研究所
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