Polarized distribution of ion channels within microdomains of the axon initial segment
Polarized distribution of ion channels within microdomains of the axon initial segment
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DOI：
10.1002/cne.21173
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发表时间：
2007-01-10
影响因子：
2.5
通讯作者：
Matthews, Gary
中科院分区：
文献类型：
--
作者：
Van Wart, Audra;Trimmer, James S.;Matthews, Gary
电压门控钠（Na-v）通道在轴突起始段（IS）处积累，其中它们的高密度支持尖峰起始。维持这种高密度的Na-v通道涉及一种大分子复合物，该复合物包括细胞骨架连接蛋白anks-G，已知唯一的蛋白质结合Na-v通道并将其定位在IS。我们先前发现Na（v）1.6是成年啮齿动物视网膜神经节细胞IS的主要Na-v通道亚型。然而，在这里，我们报告说，Na（v）1.6免疫染色是一贯减少或缺乏在短区域的IS近端的索马，虽然这两个抗-G和泛-Na-V抗体染色这一地区。我们发现，这近端IS亚区是一个独特的轴突微域，含有积累的Na（V）1.1通道，空间上隔离的Na（V）1.6通道的远端IS。此外，我们发现轴突K（v）1.2钾通道存在于远端IS内，但也被排除在Na（v）1.1富集的近端IS微区之外。由于在IS的近端和远端亚室中，锚定蛋白-G都很突出，分别与Na（v）1.1或Na（v）1.6共定位，因此与锚定蛋白-G相关以外的机制必须介导Na-v通道亚型的差异靶向，以实现IS内观察到的空间精度。轴突起始段内离子通道的这种精确排列可能是神经节细胞和其他哺乳动物神经元放电特性的重要决定因素。
Voltage-gated sodium (Na-v) channels accumulate at the axon initial segment (IS), where their high density supports spike initiation. Maintenance of this high density of Na-v channels involves a macromolecular complex that includes the cytoskeletal linker protein ankyrin-G, the only protein known to bind Na-v channels and localize them at the IS. We found previously that Na(v)1.6 is the predominant Na-v channel isoform at IS of adult rodent retinal ganglion cells. However, here we report that Na(v)1.6 immunostaining is consistently reduced or absent in short regions of the IS proximal to the soma, although both ankyrin-G and pan-Na-v antibodies stain this region. We show that this proximal IS subregion is a unique axonal microdomain, containing an accumulation of Na(v)1.1 channels that are spatially segregated from the Na(v)1.6 channels of the distal IS. Additionally, we find that axonal K(v)1.2 potassium channels are present within the distal IS, but are also excluded from the Na(v)1.1-enriched proximal IS microdomain. Because ankyrin-G was prominent in both proximal and distal subcompartments of the IS, where it colocalized with either Na(v)1.1 or Na(v)1.6, respectively, mechanisms other than association with ankyrin-G must mediate differential targeting of Na-v channel subtypes to achieve the spatial precision observed within the IS. This precise arrangement of ion channels within the axon initial segment is likely an important determinant of the firing properties of ganglion cells and other mammalian neurons.