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首页> 外文期刊>Journal of Neurophysiology >K(V)1 channels identified in rodent myelinated axons, linked to Cx29 in innermost myelin: support for electrically active myelin in mammalian saltatory conduction
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K(V)1 channels identified in rodent myelinated axons, linked to Cx29 in innermost myelin: support for electrically active myelin in mammalian saltatory conduction

机译:在啮齿动物有髓轴突中识别出的K(V)1通道,与最里面的髓磷脂中的Cx29链接:支持哺乳动物盐碱化传导中的电活性髓磷脂

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Saltatory conduction in mammalian myelinated axons was thought to be well understood before recent discoveries revealed unexpected subcellular distributions and molecular identities of the K+-conductance pathways that provide for rapid axonal repolarization. In this study, we visualize, identify, localize, quantify, and ultrastructurally characterize axonal K(V)1.1/K(V)1.2 channels in sciatic nerves of rodents. With the use of light microscopic immunocytochemistry and freeze-fracture replica immunogold labeling electron microscopy, K(V)1.1/K(V)1.2 channels are localized to three anatomically and compositionally distinct domains in the internodal axolemmas of large myelinated axons, where they form densely packed "rosettes" of 9-nm intramembrane particles. These axolemmal K(V)1.1/K(V)1.2 rosettes are precisely aligned with and ultrastructurally coupled to connexin29 (Cx29) channels, also in matching rosettes, in the surrounding juxtaparanodal myelin collars and along the inner mesaxon. As >98% of transmembrane proteins large enough to represent ion channels in these specialized domains, similar to 500,000 K(V)1.1/K(V)1.2 channels define the paired juxtaparanodal regions as exclusive membrane domains for the voltage-gated K+ conductance that underlies rapid axonal repolarization in mammals. The 1: 1 molecular linkage of K(V)1 channels to Cx29 channels in the apposed juxtaparanodal collars, plus their linkage to an additional 250,000-400,000 Cx29 channels along each inner mesaxon in every large-diameter myelinated axon examined, supports previously proposed K+ conductance directly from juxtaparanodal axoplasm into juxtaparanodal myeloplasm in mammalian axons. With neither Cx29 protein nor myelin rosettes detectable in frog myelinated axons, these data showing axon-to-myelin linkage by abundant K(V)1/Cx29 channels in rodent axons support renewed consideration of an electrically active role for myelin in increasing both saltatory conduction velocity and maximum propagation frequency in mammalian myelinated axons.
机译:在最近的发现揭示出意想不到的亚细胞分布和提供快速轴突复极化作用的K +传导途径的分子身份之前,人们认为哺乳动物髓鞘轴突的盐性传导已被很好地理解。在这项研究中,我们可视化,识别,定位,量化和超结构表征啮齿动物的坐骨神经中的轴突K(V)1.1 / K(V)1.2通道。通过使用光学显微镜免疫细胞化学和冷冻断裂复制免疫金标记电子显微镜,K(V)1.1 / K(V)1.2通道在大的髓鞘轴突的节间轴突瘤中定位于三个在解剖学和组成上不同的域9 nm膜内颗粒的密集堆积“玫瑰花”。这些轴突K(V)1.1 / K(V)1.2莲座形与连接蛋白29(Cx29)通道精确对准并超微结构耦合,这些通道也在配对莲座形中,在周围的近旁甲状旁腺髓鞘和内中轴上。由于> 98%的跨膜蛋白足够大,可以在这些特定域中代表离子通道,因此类似于500,000 K(V)1.1 / K(V)1.2通道将成对的近节旁结区域定义为电压门控K +电导的唯一膜域。是哺乳动物快速轴突复极的基础。 K(V)1通道与并置的近伞状旁突颈环中Cx29通道的1:1分子连接,以及它们在每个受检查的大直径有髓鞘轴突中沿每个中中轴的另外250,000-400,000 Cx29通道的连接,都支持先前提出的K +电导率从哺乳动物的轴突直接从近节旁的腋质转移到近节旁的髓质。在青蛙有髓轴突中均未检测到Cx29蛋白或髓鞘玫瑰花结,这些数据显示在啮齿动物轴突中通过大量K(V)1 / Cx29通道形成的轴突与髓鞘的连接支持重新考虑了髓鞘在增加盐分传导中的电活性作用髓鞘轴突的速度和最大传播频率。

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