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

被引:303
作者
Gao, J
Duan, B
Wang, DG
Deng, XH
Zhang, GY
Xu, L
Xu, TL [1 ]
机构
[1] Chinese Acad Sci, Inst Neurosci, Shanghai 200031, Peoples R China
[2] Chinese Acad Sci, Key Lab Neurobiol, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China
[3] Univ Sci & Technol China, Hefei 230027, Peoples R China
[4] Xuzhou Med Coll, Res Ctr Biochem & Mol Biol, Xuzhou 221002, Peoples R China
[5] Chinese Acad Sci, Kunming Inst Zool, Lab Learning & Memory, Kunming 650223, Peoples R China
基金
中国国家自然科学基金; 中国博士后科学基金;
关键词
D O I
10.1016/j.neuron.2005.10.011
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
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.
引用
收藏
页码:635 / 646
页数:12
相关论文
共 50 条
[21]   Extrasynaptic NMDARs oppose synaptic NMDARs by triggering CREB shut-off and cell death pathways [J].
Hardingham, GE ;
Fukunaga, Y ;
Bading, H .
NATURE NEUROSCIENCE, 2002, 5 (05) :405-414
[22]   Lactate enhances the acid-sensing Na+ channel on ischemia-sensing neurons [J].
Immke, DC ;
McCleskey, EW .
NATURE NEUROSCIENCE, 2001, 4 (09) :869-870
[23]   Global ischemia induces expression of acid-sensing ion channel 2a in rat brain [J].
Johnson, MB ;
Jin, K ;
Minami, M ;
Chen, D ;
Simon, RP .
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 2001, 21 (06) :734-740
[24]   Acidosis enhances translocation of protein kinase C but not Ca2+/calmodulin-dependent protein kinase II to cell membranes during complete cerebral ischemia [J].
Katsura, K ;
Kurihara, J ;
Siesjö, BK ;
Wieloch, T .
BRAIN RESEARCH, 1999, 849 (1-2) :119-127
[25]   Mechanisms of ischemic preconditioning effects on Ca2+ paradox-induced changes in heart [J].
Kawabata, K ;
Netticadan, T ;
Osada, M ;
Tamura, K ;
Dhalla, NS .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2000, 278 (03) :H1008-H1015
[26]   QUANTITATIVE-DETERMINATION OF GLUTAMATE MEDIATED CORTICAL NEURONAL INJURY IN CELL-CULTURE BY LACTATE-DEHYDROGENASE EFFLUX ASSAY [J].
KOH, JY ;
CHOI, DW .
JOURNAL OF NEUROSCIENCE METHODS, 1987, 20 (01) :83-90
[27]   The ASICs: Signaling molecules? Modulators? [J].
Krishtal, O .
TRENDS IN NEUROSCIENCES, 2003, 26 (09) :477-483
[28]   Expression of NMDA receptor NR1, NR2A and NR2B subunit mRNAs during development of the human hippocampal formation [J].
Law, AJ ;
Weickert, CS ;
Webster, MJ ;
Herman, MM ;
Kleinman, JE ;
Harrison, PJ .
EUROPEAN JOURNAL OF NEUROSCIENCE, 2003, 18 (05) :1197-1205
[29]   cAMP-dependent protein kinase phosphorylation of the acid-sensing ion channel-1 regulates its binding to the protein interacting with C-kinase-1 [J].
Leonard, AS ;
Yermolaieva, O ;
Hruska-Hageman, A ;
Askwith, CC ;
Price, MP ;
Wemmie, JA ;
Welsh, MJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (04) :2029-2034
[30]   Calcium/calmodulin-dependent protein kinase II is associated with the N-methyl-D-aspartate receptor [J].
Leonard, AS ;
Lim, IA ;
Hemsworth, DE ;
Horne, MC ;
Hell, JW .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (06) :3239-3244