Glutamate receptor channels in hippocampal neurons and their development

哺乳动物中枢神经系统谷氨酸受体通道可分为三种亚型；NMDA, AMPA/kainate （KA）和KA选择性受体通道。AMPA/KA受体通道同时被AMPA和KA激活。在本研究中，我们主要研究了AMPA/KA受体的特性及其在17 ~ 19日龄大鼠胚胎培养的大鼠海马神经元中的发育。结果总结如下：1)培养海马神经元对KA和AMPA的敏感性在镀后7天内形成。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 -感应电流幅值逐渐增大。2) AMPA/KA受体分为两类。I型受体表现出外向整流的电流-电压（I- v）关系，Ca^<2+>磁导率很小。相比之下，II型受体具有显著的向内整流和显著的Ca^<2+>通透性。结合全细胞膜片钳记录和单个神经元mRNA的PCR扩增，我们确定了海马神经元中表达的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)ⅱ型AMPA/KA受体在1 ~ 5周内只出现在椭圆体和细神经突的小神经元中。这些神经元似乎是GABA能的中间神经元，因为在这些神经元中检测到广泛性焦虑症。4)当解离的CA1锥体细胞与CA3/CA4区神经元之间建立兴奋性突触时，在突触后CA1神经元的顶端树突上检测到高密度的AMPA斑点。这些点上的快速EPSC和AMPA响应几乎呈线性I-V关系。这表明I型AMPA/KA受体比II型AMPA/KA受体更负责在这种兴奋性突触中产生快速EPSC。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