Glutamate receptor channels in hippocampal neurons and their development

哺乳动物中枢神经系统中的谷氨酸受体通道分为三种亚型：NMDA通道、AMPA/KA(KA)通道和KA选择性受体通道。AMPA/KA受体通道被AMPA和KA激活。在这项研究中，我们主要研究了AMPA/KA受体的特性及其在培养的17-19日龄大鼠胚胎海马神经元中的发育。研究结果总结如下。1)培养的海马神经元在接种后7d内对KA和AMPA敏感。这是由于AMPA/KA受体的发育，而不是KA选择性受体的发育。此后，KA或AMPA诱发电流的幅度逐渐增大。2)AMPA/KA受体分为两类。I型受体呈外向整流电流-电压(I-V)关系，钙离子通透性很小。相反，II型受体的特征是显著的内向整流和显著的钙离子通透性。C…结合更多的全细胞膜片钳记录和单个神经元mRNA的聚合酶链式反应扩增，我们确定了海马神经元表达的I型和II型AMPA/KA受体的亚基组成。I型受体由GluR1和GluR2亚基组成，而II型受体由GluR1和GluR4亚基组成。3)植入后1~5周，II型AMPA/KA受体仅见于胞体椭圆形的小神经元和细小的突起。这些神经元似乎是GABA能中间神经元，因为在这些神经元中检测到GAD。4)分离的CA1区锥体细胞与CA3/CA4区神经元建立兴奋性突触后，突触后CA1区神经元的顶端树突上可见高密度的AMPA斑点。这些斑点的快速EPSC和AMPA反应几乎都呈线性的I-V关系。这表明，在兴奋性突触中，I型AMPA/KA受体比II型AMPA/KA受体更负责产生快速EPSC。较少

Glutamate receptor channels in the mammalian central nervous system are classified into three subtypes; NMDA, AMPA/kainate (KA) and KA-selective receptor channels. AMPA/KA receptor channels are activated by both AMPA and KA. In this study, we investigated mainly the properties of AMPA/KA receptors and their development in cultured rat hippocampal neurons prepared from 17- to 19-day-old rat embryos. The results are summarized as follows. 1) Cultured hippocampal neurons became sensitive to KA and AMPA within 7 days after plating. This is due to the development of AMPA/KA receptors, but not of KA-selective receptors. Thereafter, the amplitude of KA- or AMPA-induced current increased gradually. 2) AMPA/KA receptors were classified into two types. The type I receptor exhibited an outwardly-rectifying current-voltage (I-V) relation with little Ca^<2+> permeability. In contrast, the type II receptor was characterized by a remarkable inward rectification and a prominent Ca^<2+> permeability. C … More ombining whole-cell patch-clamp recordings and the PCR amplification of the mRNA harvested from a single neuron, we determined the subunit composition of the type I and type II AMPA/KA receptors expressed in hippocampal neurons. The type I receptor was composed of the GluR1 and GluR2 subunits, whereas the type II receptor of the GluR1 and GluR4 subunits. 3) The type II AMPA/KA receptor appeared exclusively in small neurons with elliptical somata and fine neurites throughout 1-5 weeks after plating. These neurons seem to be GABA ergic interneurons, since GAD was detected in these neurons. 4) When the excitatory synapse was established between dissociated CA1 pyramidal cells and neurons from the CA3/CA4 regions, high-density AMPA spots were detected on the apical dendrite of the postsynaptic CA1 neuron. Both the fast EPSC and the AMPA response on these spots showed almost linear I-V relations. This suggests that the type I AMPA/KA receptor is more responsible for generating the fast EPSC in this excitatory synapse than the type II AMPA/KA receptor. Less