Coupling between NMDA receptor and acid-sensing ion channel contributes to ischemic neuronal death

	Coupling between NMDA receptor and acid-sensing ion channel contributes to ischemic neuronal death
	Gao J 1,2; Duan B 1,2; Wang DG 1,2; Deng XH 1; Zhang GY 3; Xu L 4; Xu TL*1,2; tlxu@ion.ac.cn
	2005
发表期刊	NEURON
ISSN	0896-6273
卷号	48 期号:4 页码:635-646
合作性质	其它
摘要	Acid-sensing ion channels (ASICs) composed of ASIC1a subunit exhibit a high Ca2+ permeability and play important roles in synaptic plasticity and acid-induced cell death. Here, we show that ischemia enhances ASIC currents through the phosphorylation at Ser478 and Ser479 of ASIC1a, leading to exacerbated ischemic cell death. The phosphorylation is catalyzed by Ca2+/calmodulin-dependent protein kinase II (CaMKII) activity, as a result of activation of NR2B-containing N-methyl-D-aspartate subtype of glutamate receptors (NMDARs) during ischemia. Furthermore, NR2B-specific antagonist, CaMKII inhibitor, or overexpression of mutated form of ASIC1a with Ser478 or Ser479 replaced by alanine (ASICla-S478A, ASIC1a-S479A) in cultured hippocampal neurons prevented ischemia-induced enhancement of ASIC currents, cytoplasmic Ca2+ elevation, as well as neuronal death. Thus, NMDAR-CaMKII cascade is functionally coupled to ASICs and contributes to acidotoxicity during ischemia. Specific blockade of NMDAR/CaMKII-ASIC coupling may reduce neuronal death after ischemia and other pathological conditions involving excessive glutamate release and acidosis.
资助者	This study was supported by the National Natural Science Founda- tion of China (Nos. Grants 30125015, 30321002), the National Basic Research Program of China (No. 2006CB500803), and the Knowl- edge Innovation Projects from the Chinese Academy of Sciences (KSCX 2-SW-217). J.G. is supported by the China Postdoctoral Sci- ence Foundation and the K.C. Wong Education Foundation. ; This study was supported by the National Natural Science Founda- tion of China (Nos. Grants 30125015, 30321002), the National Basic Research Program of China (No. 2006CB500803), and the Knowl- edge Innovation Projects from the Chinese Academy of Sciences (KSCX 2-SW-217). J.G. is supported by the China Postdoctoral Sci- ence Foundation and the K.C. Wong Education Foundation. ; This study was supported by the National Natural Science Founda- tion of China (Nos. Grants 30125015, 30321002), the National Basic Research Program of China (No. 2006CB500803), and the Knowl- edge Innovation Projects from the Chinese Academy of Sciences (KSCX 2-SW-217). J.G. is supported by the China Postdoctoral Sci- ence Foundation and the K.C. Wong Education Foundation. ; This study was supported by the National Natural Science Founda- tion of China (Nos. Grants 30125015, 30321002), the National Basic Research Program of China (No. 2006CB500803), and the Knowl- edge Innovation Projects from the Chinese Academy of Sciences (KSCX 2-SW-217). J.G. is supported by the China Postdoctoral Sci- ence Foundation and the K.C. Wong Education Foundation.
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收录类别	SCI
语种	英语
资助者	This study was supported by the National Natural Science Founda- tion of China (Nos. Grants 30125015, 30321002), the National Basic Research Program of China (No. 2006CB500803), and the Knowl- edge Innovation Projects from the Chinese Academy of Sciences (KSCX 2-SW-217). J.G. is supported by the China Postdoctoral Sci- ence Foundation and the K.C. Wong Education Foundation. ; This study was supported by the National Natural Science Founda- tion of China (Nos. Grants 30125015, 30321002), the National Basic Research Program of China (No. 2006CB500803), and the Knowl- edge Innovation Projects from the Chinese Academy of Sciences (KSCX 2-SW-217). J.G. is supported by the China Postdoctoral Sci- ence Foundation and the K.C. Wong Education Foundation. ; This study was supported by the National Natural Science Founda- tion of China (Nos. Grants 30125015, 30321002), the National Basic Research Program of China (No. 2006CB500803), and the Knowl- edge Innovation Projects from the Chinese Academy of Sciences (KSCX 2-SW-217). J.G. is supported by the China Postdoctoral Sci- ence Foundation and the K.C. Wong Education Foundation. ; This study was supported by the National Natural Science Founda- tion of China (Nos. Grants 30125015, 30321002), the National Basic Research Program of China (No. 2006CB500803), and the Knowl- edge Innovation Projects from the Chinese Academy of Sciences (KSCX 2-SW-217). J.G. is supported by the China Postdoctoral Sci- ence Foundation and the K.C. Wong Education Foundation.
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/5863
专题	科研部门_学习记忆的分子神经机制（徐林）
通讯作者	tlxu@ion.ac.cn
作者单位	1.Institute of Neuroscience and Key Laboratory of Neurobiology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai 200031 China 2.School of Life Sciences University of Science and Technology of China Hefei 230027 China 3.Research Center for Biochemistry and Molecular Biology Xuzhou Medical College Xuzhou 221002 China 4.Laboratory of Learning and Memory Kunming Institute of Zoology Chinese Academy of Sciences Kunming 650223 China
推荐引用方式 GB/T 7714	Gao J,Duan B,Wang DG,et al. Coupling between NMDA receptor and acid-sensing ion channel contributes to ischemic neuronal death[J]. NEURON,2005,48(4):635-646.
APA	Gao J.,Duan B.,Wang DG.,Deng XH.,Zhang GY.,...&tlxu@ion.ac.cn.(2005).Coupling between NMDA receptor and acid-sensing ion channel contributes to ischemic neuronal death.NEURON,48(4),635-646.
MLA	Gao J,et al."Coupling between NMDA receptor and acid-sensing ion channel contributes to ischemic neuronal death".NEURON 48.4(2005):635-646.

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