Numbers, densities, and colocalization of AMPA- and NMDA-type glutamate receptors at individual synapses in the superficial spinal dorsal horn of rats

Numbers, densities, and colocalization of AMPA- and NMDA-type glutamate receptors at individual synapses in the superficial spinal dorsal horn of rats
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DOI:
10.1523/jneurosci.1551-08.2008
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发表时间:
2008-09-24
影响因子:
5.3
通讯作者:
Shigemoto, Ryuichi
Shigemoto, Ryuichi
中科院分区:
医学1区
文献类型:
--
作者:
Antal, Miklos;Fukazawa, Yugo;Shigemoto, Ryuichi

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离子型谷氨酸受体在脊髓对伤害性感觉信号的处理和慢性痛中枢敏感化的诱导中起重要作用。在这里,我们应用高度敏感的冷冻断裂复制品标记到大鼠脊髓背角的I-II层,并研究了AMPA和NMDA型谷氨酸受体的数量,密度和共定位在单个突触后膜专业化与高分辨率。在Ⅰ-Ⅱ层的突触后膜中,AMPA受体全部表达,其中大部分(96%)也表达NMDA受体NR 1亚基。单个突触后膜上AMPA和NMDA受体的金颗粒数量与突触后膜特化的大小呈线性相关,其范围为8-214和5-232,中值为37和28,密度变化范围为325-3365个/μ m(2)和102-2263个/μ m(2),中位数分别为1115个/μ m(2)和777个/μ m(2)。几乎所有(99%)的谷氨酸能突触后膜表达GluR 2,其中大多数(87%)也免疫反应GluR 1。泛AMPA,NR 1和GluR 2亚基的金颗粒的数量与突触后表面积的大小呈线性相关。关于GluR 1,可能有两个群体的突触与高和低GluR 1密度。在大于0.1 μ m(2)的突触中,GluR 1亚基的恢复数量非常少。GluR 1和GluR 2亚基的差异表达表明AMPA受体亚基的组成通过突触前机制进行调节。
Ionotropic glutamate receptors play important roles in spinal processing of nociceptive sensory signals and induction of central sensitization in chronic pain. Here we applied highly sensitive freeze-fracture replica labeling to laminae I-II of the spinal dorsal horn of rats and investigated the numbers, densities, and colocalization of AMPA- and NMDA-type glutamate receptors at individual postsynaptic membrane specializations with a high resolution. All glutamatergic postsynaptic membranes in laminae I-II expressed AMPA receptors, and most of them (96%) were also immunoreactive for the NR1 subunit of NMDA receptors. The numbers of gold particles for AMPA and NMDA receptors at individual postsynaptic membranes showed a linear correlation with the size of postsynaptic membrane specializations and varied in the range of 8-214 and 5-232 with median values of 37 and 28, whereas their densities varied in the range of 325-3365/mu m(2) and 102-2263/mu m(2) with median values of 1115/mu m(2) and 777/mu m(2), respectively. Virtually all (99%) glutamatergic postsynaptic membranes expressed GluR2, and most of them (87%) were also immunoreactive for GluR1. The numbers of gold particles for pan-AMPA, NR1, and GluR2 subunits showed a linear correlation with the size of postsynaptic surface areas. Concerning GluR1, there may be two populations of synapses with high and low GluR1 densities. In synapses larger than 0.1 mu m(2), GluR1 subunits were recovered in very low numbers. Differential expression of GluR1 and GluR2 subunits suggests regulation of AMPA receptor subunit composition by presynaptic mechanism.