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Title: A Nonproton Ligand Sensor in the Acid-Sensing Ion Channel
Author: Yu, Ye ; Chen, Zhi ; Li, Wei-Guang ; Cao, Hui ; Feng, En-Guang ; Yu, Fang ; Liu, Hong ; Jiang, Hualiang ; Xu, Tian-Le(徐天乐)
Source: NEURON
Issued Date: 2010
Volume: 68, Issue:1, Pages:61-72
Keyword: TARANTULA TOXIN PSALMOTOXIN-1 ; DORSAL-HORN NEURONS ; TRP CHANNELS ; MECHANOSENSORY FUNCTION ; EXTRACELLULAR DOMAIN ; INFLAMMATORY PAIN ; ASIC 1A ; MODULATION ; ISCHEMIA ; CA2+
Subject: Neurosciences & Neurology
Corresponding Author: 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
English Abstract: 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.
Indexed Type: SCI
Language: 英语
Content Type: 期刊论文
URI: http://ir.sibs.ac.cn/handle/331001/1568
Appears in Collections:神经所(总)_期刊论文

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Yu, Ye; Chen, Zhi; Li, Wei-Guang; Cao, Hui; Feng, En-Guang; Yu, Fang; Liu, Hong; Jiang, Hualiang; Xu, Tian-Le.A Nonproton Ligand Sensor in the Acid-Sensing Ion Channel,NEURON,2010,68(1):61-72
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