Wang H, Allen M L, Grigg J J, Noebels J L, Tempel B L
Department of Otolaryngology-Head and Neck Surgery, University of Washington School of Medicine, Seattle 98195, USA.
Neuron. 1995 Dec;15(6):1337-47. doi: 10.1016/0896-6273(95)90012-8.
Voltage-gated K+ channels are localized to juxtaparanodal regions of myelinated axons. To begin to understand the role of normal compact myelin in this localization, we examined mKv1.1 and mKv1.2 expression in the dysmyelinating mouse mutants shiverer and Trembler. In neonatal wild-type and shiverer mice, the focal localization of both proteins in axon fiber tracts is similar, suggesting that cues other than mature myelin can direct initial K+ channel localization in shiverer mutants. In contrast, K+ channel localization is altered in hypomyelinated axonal fiber tracts of adult mutants, suggesting that abnormal myelination leads to channel redistribution. In shiverer adult, K+ channel expression is up-regulated in both axons and glia, as revealed by immunocytochemistry, RNase protection, and in situ hybridization studies. This up-regulation of K+ channels in hypomyelinated axon tracts may reflect a compensatory reorganization of ionic currents, allowing impulse conduction to occur in these dysmyelinating mouse mutants.
电压门控钾离子通道定位于有髓轴突的近节旁区域。为了初步了解正常紧密髓鞘在这种定位中的作用，我们检测了脱髓鞘小鼠突变体颤抖鼠（shiverer）和震颤鼠（Trembler）中mKv1.1和mKv1.2的表达。在新生野生型和颤抖鼠小鼠中，两种蛋白在轴突纤维束中的局灶定位相似，这表明除了成熟髓鞘之外的线索可以指导颤抖鼠突变体中钾离子通道的初始定位。相比之下，成年突变体的髓鞘减少的轴突纤维束中钾离子通道定位发生改变，这表明异常髓鞘形成会导致通道重新分布。免疫细胞化学、核糖核酸酶保护和原位杂交研究表明，在成年颤抖鼠中，轴突和神经胶质细胞中的钾离子通道表达均上调。髓鞘减少的轴突束中钾离子通道的这种上调可能反映了离子电流的代偿性重组，从而使这些脱髓鞘小鼠突变体能够进行冲动传导。
