Compartment-dependent colocalization of Kir3.2-containing K+ channels and GABAB receptors in hippocampal pyramidal cells

Compartment-dependent colocalization of Kir3.2-containing K+ channels and GABAB receptors in hippocampal pyramidal cells
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DOI:
10.1523/jneurosci.4178-05.2006
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发表时间:
2006-04-19
影响因子:
5.3
通讯作者:
Shigemoto, R
Shigemoto, R
中科院分区:
医学1区
文献类型:
--
作者:
Kulik, A;Vida, I;Shigemoto, R

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G蛋白偶联内向整流钾通道(Kir 3通道)与亲代谢型GABA(B)受体偶联,对神经元兴奋的控制至关重要。为了确定Kir 3通道的分布及其与海马锥体细胞上GABAB受体的空间关系,我们使用了高分辨率免疫细胞化学方法。Kir3.2亚基的免疫反应是最丰富的突触后和本地化的突触外质膜的树突状轴和刺的主细胞。Kir3.2的免疫金颗粒的定量分析揭示了在树突棘上推定的突触能突触周围的蛋白质富集,类似于GABA(B1)。与此观察结果一致,Kir3.2和GABAB 1的高度共聚揭示了兴奋性突触周围的高度敏感的SDS消化冷冻断裂复制免疫标记。相反,在树突状轴受体和通道被发现主要是隔离。这些结果表明,Kir3.2-含有K+通道的树突棘优先介导的GABA的效果,而树突轴上的通道很可能被激活的其他神经递质以及。因此,Kir 3通道,定位于海马主细胞的不同亚细胞区室,似乎是差异参与锥体细胞树突的突触整合。
G-protein-coupled inwardly rectifying K+ channels (Kir3 channels) coupled to metabotropic GABA(B) receptors are essential for the control of neuronal excitation. To determine the distribution of Kir3 channels and their spatial relationship to GABAB receptors on hippocampal pyramidal cells, we used a high-resolution immunocytochemical approach. Immunoreactivity for the Kir3.2 subunit was most abundant postsynaptically and localized to the extrasynaptic plasma membrane of dendritic shafts and spines of principal cells. Quantitative analysis of immunogold particles for Kir3.2 revealed an enrichment of the protein around putative glutamatergic synapses on dendritic spines, similar to that of GABA(B1). Consistent with this observation, a high degree of coclustering of Kir3.2 and GABAB1 was revealed around excitatory synapses by the highly sensitive SDS-digested freeze-fracture replica immunolabeling. In contrast, in dendritic shafts receptors and channels were found to be mainly segregated. These results suggest that Kir3.2-containing K+ channels on dendritic spines preferentially mediate the effect of GABA, whereas channels on dendritic shafts are likely to be activated by other neurotransmitters as well. Thus, Kir3 channels, localized to different subcellular compartments of hippocampal principal cells, appear to be differentially involved in synaptic integration in pyramidal cell dendrites.