Westenbroek R E, Noebels J L, Catterall W A
Department of Pharmacology, University of Washington, Seattle 98195.
J Neurosci. 1992 Jun;12(6):2259-67. doi: 10.1523/JNEUROSCI.12-06-02259.1992.
Type I and type III Na+ channels are localized mainly in neuronal cell bodies in mouse brain. Type II channels are preferentially localized in unmyelinated fiber tracts but are not detectable in normally myelinated fibers. In shiverer mice, which lack compact myelin due to a defect in the myelin basic protein gene, elevated expression of type II Na+ channels was observed in the hypomyelinated axons of large-caliber fiber tracts such as the corpus callosum, internal capsule, fimbria, fornix, corpus medullare of the cerebellum, and nigrostriatal pathway by immunocytochemical analysis with subtype-specific antibodies. No difference was observed in the localization of type I and type III Na+ channels between wild-type and shiverer mice. These findings support the hypothesis that type II Na+ channels are preferentially localized in axons of brain neurons and suggest that their density and localization are regulated by myelination. The selective increase in the number of type II channels in hypomyelinated fiber tracts may contribute to the hyperexcitable phenotype of the shiverer mouse.
I型和III型钠离子通道主要定位于小鼠大脑的神经元细胞体。II型通道优先定位于无髓纤维束，但在正常有髓纤维中无法检测到。在由于髓鞘碱性蛋白基因缺陷而缺乏致密髓鞘的颤抖小鼠中，通过使用亚型特异性抗体的免疫细胞化学分析，在诸如胼胝体、内囊、伞、穹窿、小脑髓体和黑质纹状体通路等大口径纤维束的髓鞘发育不全的轴突中观察到II型钠离子通道的表达升高。在野生型和颤抖小鼠之间，I型和III型钠离子通道的定位没有差异。这些发现支持了II型钠离子通道优先定位于脑神经元轴突的假说，并表明它们的密度和定位受髓鞘形成的调节。髓鞘发育不全的纤维束中II型通道数量的选择性增加可能导致颤抖小鼠的兴奋性过高表型。
