钠离子通道 β4 亚基在无髓纤维中的单一定位及其在纹状体中的作用。

Singular localization of sodium channel β4 subunit in unmyelinated fibres and its role in the striatum.

机构信息

1] Department of Neuroscience for Neurodegenerative Disorders, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan [2] Laboratory for Structural Neuropathology, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan [3] Laboratory for Molecular Mechanisms of Thalamus Development, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan [4] CREST (Core Research for Evolutionary Science and Technology), JST, 7 Gobancho, Chiyoda-ku, Tokyo 102-0076, Japan.

1] Laboratory for Structural Neuropathology, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan [2] Department of Applied Chemistry, Kogakuin University, 2665-1 Nakano-cho, Hachioji, Tokyo 192-0015, Japan.

出版信息

Nat Commun. 2014 Nov 21;5:5525. doi: 10.1038/ncomms6525.

DOI:10.1038/ncomms6525

PMID:25413837

Abstract

Voltage-gated Na(+) channel β-subunits are multifunctional molecules that modulate Na(+) channel activity and regulate cell adhesion, migration and neurite outgrowth. β-subunits including β4 are known to be highly concentrated in the nodes of Ranvier and axon initial segments in myelinated axons. Here we show diffuse β4 localization in striatal projection fibres using transgenic mice that express fluorescent protein in those fibres. These axons are unmyelinated, forming large, inhibitory fibre bundles. Furthermore, we report β4 dimer expression in the mouse brain, with high levels of β4 dimers in the striatal projection fascicles, suggesting a specific role of β4 in those fibres. Scn4b-deficient mice show a resurgent Na(+) current reduction, decreased repetitive firing frequency in medium spiny neurons and increased failure rates of inhibitory postsynaptic currents evoked with repetitive stimulation, indicating an in vivo channel regulatory role of β4 in the striatum.

摘要

电压门控钠 (Na+) 通道 β 亚基是多功能分子，可调节 Na+ 通道活性并调节细胞黏附、迁移和轴突生长。β 亚基（包括 β4）已知在有髓轴突的郎飞结和轴突起始段高度集中。在这里，我们使用在这些纤维中表达荧光蛋白的转基因小鼠显示纹状体投射纤维中 β4 的弥散定位。这些轴突没有髓鞘，形成大的抑制性纤维束。此外，我们报告了在小鼠脑中 β4 二聚体的表达，在纹状体投射束中有高水平的 β4 二聚体，表明 β4 在这些纤维中有特定的作用。Scn4b 缺陷型小鼠显示出钠电流恢复性减少、中间棘神经元重复放电频率降低以及重复刺激诱发的抑制性突触后电流失败率增加，表明 β4 在纹状体中具有体内通道调节作用。