He Y, Janssen W G, Vissavajjhala P, Morrison J H
Neurobiology of Aging Laboratory, Mount Sinai School of Medicine, New York, New York 10029, USA.
Exp Neurol. 1998 Mar;150(1):1-13. doi: 10.1006/exnr.1997.6720.
GluR2 is the regulatory subunit in the AMPA family of glutamate receptors (GluRs) in that its presence inhibits calcium flux and dominates the current/ voltage characteristics of AMPA receptors. Studies from other laboratories have shown that GABAergic interneurons have a lower ratio of GluR2/GluR1 mRNA than pyramidal cells as well as possessing AMPA receptors that have a higher relative permeability to calcium. We hypothesized that such differences might be related to differences in the subunit stoichiometry at the AMPA synapses in each cell class, and used a GluR2-specific monoclonal antibody in a double-label immunogold protocol with anti-GABA and anti-CaM kinase II to compare the GluR2 representation at asymmetric synapses in GABA neurons to that of pyramidal cells in rat CA1. Virtually all CA1 pyramidal cells as well as the majority of GABAergic interneurons were GluR2 positive. EM immunogold labeling also showed that GABAergic interneurons had distinctive ultrastructural features and contained GluR2 in both their soma and their dendrites, as did the spines and shafts of pyramidal cells. GluR2 immunoreactivity was frequently preferentially located at asymmetric synapses on both pyramidal cell spines and shafts as well as the dendritic processes and soma of GABAergic interneurons. However, the labeled synapses on GABAergic neurons had a significantly lower number of immunogold particles than those on pyramidal cells. In fact, 90% of the labeled asymmetric synapses on GABAergic cells had one to three gold particles, whereas greater than 70% of the labeled asymmetric synapses on pyramidal cells had four or more gold particles associated with the synapse. These data suggest that while both cell classes contain GluR2, they differ in the relative representation of GluR2 at their AMPA synapses, such that GABAergic neurons might possess AMPA receptors with higher calcium permeability on average than pyramidal cells. Such differences in subunit representation at AMPA-receptor-mediated synapses would not only lead to differences in calcium permeability and functional characteristics across these two cell classes, but might also be relevant to the hippocampal patterns of selective vulnerability with respect to excitotoxicity and neurodegeneration.
GluR2是谷氨酸受体（GluRs）AMPA家族中的调节亚基，因为它的存在会抑制钙内流，并决定AMPA受体的电流/电压特性。其他实验室的研究表明，GABA能中间神经元的GluR2/GluR1 mRNA比值低于锥体细胞，并且其AMPA受体对钙的相对通透性更高。我们推测，这种差异可能与每个细胞类型的AMPA突触处亚基化学计量的差异有关，并在与抗GABA和抗钙调蛋白激酶II的双重标记免疫金实验中使用GluR2特异性单克隆抗体，以比较GABA神经元中不对称突触处的GluR2表达与大鼠CA1区锥体细胞的GluR2表达。几乎所有的CA1锥体细胞以及大多数GABA能中间神经元的GluR2均呈阳性。电子显微镜免疫金标记还显示，GABA能中间神经元具有独特的超微结构特征，其胞体和树突中均含有GluR2，锥体细胞的棘突和轴突也是如此。GluR2免疫反应性通常优先位于锥体细胞棘突和轴突以及GABA能中间神经元的树突过程和胞体上的不对称突触处。然而，GABA能神经元上标记的突触的免疫金颗粒数量明显低于锥体细胞上的突触。事实上，GABA能细胞上90%的标记不对称突触有1至3个金颗粒，而锥体细胞上超过70%的标记不对称突触有4个或更多与突触相关的金颗粒。这些数据表明，虽然这两种细胞类型都含有GluR2，但它们在AMPA突触处GluR2的相对表达有所不同，因此GABA能神经元平均可能拥有比锥体细胞更高钙通透性的AMPA受体。AMPA受体介导的突触处亚基表达的这种差异不仅会导致这两种细胞类型在钙通透性和功能特性上的差异，还可能与海马体在兴奋性毒性和神经退行性变方面选择性易损性的模式有关。
