期刊
JOURNAL OF PHYSIOLOGY-LONDON
卷 586, 期 3, 页码 739-750出版社
WILEY
DOI: 10.1113/jphysiol.2007.144618
关键词
-
资金
- Biotechnology and Biological Sciences Research Council [BB/D015286/1, BB/D015782/1] Funding Source: researchfish
- Medical Research Council [G0601812] Funding Source: researchfish
- Biotechnology and Biological Sciences Research Council [BB/D015782/1, BB/D015286/1] Funding Source: Medline
- Medical Research Council [G0601812] Funding Source: Medline
- NIMH NIH HHS [R01 MH060252-07, MH060252-05A2, R01 MH060252] Funding Source: Medline
- BBSRC [BB/D015782/1, BB/D015286/1] Funding Source: UKRI
- MRC [G0601812] Funding Source: UKRI
NMDA receptors are present at glutamatergic synapses throughout the brain, and are important for the development and plasticity of neural circuits. Their subunit composition is developmentally regulated. We have investigated the developmental profile of functional synaptic NMDA receptor subunits in dopaminergic neurones of the substantia nigra pars compacta (SNc). In SNc dopaminergic neurones from rats aged postnatal day (P)7, ifenprodil inhibited NMDA-EPSCs with an estimated IC50 of 0.36 mu m and a maximum inhibition of 73.5 +/- 2.7% (10 mu m), consistent with a substantial population of NR1/NR2B-containing diheteromeric receptors. UBP141, a novel NR2D-preferring antagonist, inhibited NMDA-EPSCs with an estimated IC50 of 6.2 mu M. During postnatal development, the maximum inhibitory effect of 10 mu m ifenprodil significantly decreased. However, NMDA-EPSCs were not inhibited by Zn2+ (200 nM) or potentiated by the Zn2+ chelator TPEN (1 mu M), and the effect of UBP141 did not increase during development, indicating that NR2B subunits are not replaced with diheteromeric NR2A or NR2D subunits. The time course of the decay of NMDA-EPSCs was not significantly changed in ifenprodil at any age tested. Together, these data suggest that diheteromeric NR1/NR2A or NR1/NR2D receptors do not account for the ifenprodil-resistant component of the NMDA-EPSC. We propose that NR1/NR2B/NR2D triheteromers form a significant fraction of synaptic NMDA receptors during postnatal development. This is the first report of data suggesting NR2D-containing triheteromeric NMDA receptors at a brain synapse.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据