Coupling between NMDA receptor and acid-sensing ion channel contributes to ischemic neuronal death
文献类型：期刊论文
| 作者 | Gao J1,2; Duan B1,2; Wang DG1,2; Deng XH1; Zhang GY3; Xu L4; Xu TL[*]1,2 |
| 刊名 | NEURON
 |
| 出版日期 | 2005 |
| 卷号 | 48期号:4页码:635-646 |
| ISSN号 | 0896-6273 |
| 通讯作者 | tlxu@ion.ac.cn |
| 合作状况 | 其它 |
| 英文摘要 | 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. |
| 收录类别 | SCI |
| 资助信息 | 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. |
| 原文出处 | 200548635.pdf |
| 语种 | 英语 |
| 公开日期 | 2010-08-24 |
| 源URL | [http://159.226.149.42:8088/handle/152453/5863]  |
| 专题 | 昆明动物研究所_学习记忆的分子神经机制 |
| 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.,...&Xu TL[*].(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. |
入库方式： OAI收割
来源：昆明动物研究所
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