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

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	Coupling between NMDA receptor and acid-sensing ion channel contributes to ischemic neuronal death
	Gao, J ; Duan, B ; Wang, DG ; Deng, XH ; Zhang, GY ; Xu, L ; Xu, TL(徐天乐)
刊名	NEURON
	2005
卷号	48 期号:4 页码:635-646
关键词	PROTEIN-KINASE-II SUBUNIT MESSENGER-RNAS D-ASPARTATE RECEPTOR CELL-DEATH FOREBRAIN ISCHEMIA GLUTAMATE NEUROTOXICITY HIPPOCAMPAL SYNAPSES GLUCOSE DEPRIVATION NERVOUS-SYSTEM NR2B SUBUNIT
ISSN号	0896-6273
通讯作者	Xu, TL (reprint author), Chinese Acad Sci, Inst Neurosci, Shanghai 200031, Peoples R China,tlxu@ion.ac.cn
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.
学科主题	Neurosciences & Neurology
收录类别	SCI
语种	英语
公开日期	2012-07-23
内容类型	期刊论文
源URL	[http://ir.sibs.ac.cn/handle/331001/1866]
专题	上海神经科学研究所_神经所(总)
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.