Functional heterogeneity of NMDA receptors in rat substantia nigra pars compacta and reticulata neurones.
Functional heterogeneity of NMDA receptors in rat substantia nigra pars compacta and reticulata neurones.
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DOI：
10.1111/j.1460-9568.2010.07298.x
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发表时间：
2010-08
期刊：
影响因子：
--
通讯作者：
Gibb AJ
中科院分区：
文献类型：
--
作者：
Suárez F;Zhao Q;Monaghan DT;Jane DE;Jones S;Gibb AJ
黑质致密部(SNC)和网状部(SNR)构成了两个功能不同的基底节主要成分。帕金森病患者黑质多巴胺能神经元易受细胞死亡的影响，NMDA受体激活是其潜在的致死机制。我们研究了出生后第7天和第28天大鼠黑质和黑质中的全细胞和突触NMDA对细胞内ATP和GTP应用的敏感性。SNR组的NMDA电流密度(pA/pF)和对长时间或重复应用NMDA的脱敏作用均大于SNC组。当不补充ATP水平时，P7 SNC DA神经元对长期给予NMDA的反应不敏感，但在P28时不变。在P28，无论有没有添加ATP，SNR神经元的脱敏程度都高于SNC神经元。对短暂的NMDA应用和突触NMDA电流的反应对吸管溶液中的ATP不敏感。为了研究SNC和SNR之间的这些差异，我们测试了NR2亚单位选择性拮抗剂。在SNR和SNR神经元上，异丙苯地尔(10μm)和UBP141(4μm)均能抑制NMDA电流，但不能被锌离子(100 Nm)抑制，提示SNR和SNR神经元表达相似的受体亚基：NR2B和NR2D，但不表达NR2A型。SNC和SNR中不同的NMDA反应特性可能是由于受体调节和/或转运的不同所致。黑质多巴胺神经元对细胞死亡的易感性与NMDA电流密度或受体亚型无关，但可能部分与NMDA受体脱敏作用不足有关。
The nigra substantia nigra pars compacta (SNc) and substantia pars reticulata (SNr) form two major basal ganglia components with different functional roles. SNc dopaminergic (DA) neurones are vulnerable to cell death in Parkinson's disease, and NMDA receptor activation is a potential contributing mechanism. We have investigated the sensitivity of whole-cell and synaptic NMDA responses to intracellular ATP and GTP application in the SNc and SNr from rats on postnatal day (P) 7 and P28. Both NMDA current density (pA/pF) and desensitization to prolonged or repeated NMDA application were greater in the SNr than in the SNc. When ATP levels were not supplemented, responses to prolonged NMDA administration desensitized in P7 SNc DA neurones but not at P28. At P28, SNr neurones desensitized more than SNc neurones, with or without added ATP. Responses to brief NMDA applications and synaptic NMDA currents were not sensitive to inclusion of ATP in the pipette solution. To investigate these differences between the SNc and SNr, NR2 subunit-selective antagonists were tested. NMDA currents were inhibited by ifenprodil (10 μm) and UBP141 (4 μm), but not by Zn2+ (100 nm), in both the SNr and SNc, suggesting that SNc and SNr neurones express similar receptor subunits; NR2B and NR2D, but not NR2A. The different NMDA response properties in the SNc and SNr may be caused by differences in receptor modulation and/or trafficking. The vulnerability of SNc DA neurones to cell death is not correlated with NMDA current density or receptor subtypes, but could in part be related to inadequate NMDA receptor desensitization.
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影响因子：
16.2
作者：
KOHR, G;ECKARDT, S;SEEBURG, PH
通讯作者：
SEEBURG, PH
影响因子：
5.5
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JOHNSON, SW;NORTH, RA
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NORTH, RA
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16.2
作者：
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通讯作者：
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作者：
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