title: Singular localization of sodium channel β4 subunit in unmyelinated fibres and its role in the striatum.
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.
authors.affiliation: 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.
authors.forename: Haruko
authors.initials: H
authors.lastname: Miyazaki
authors.affiliation: 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.
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Oyama
authors.affiliation: Neurophysiology Research Group, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo 173-0015, Japan.
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Inoue
authors.affiliation: Neurophysiology Research Group, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo 173-0015, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Aosaki
authors.affiliation: Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Developmental Biology, 2-2-3 Minatojima Minami, Chuou-ku, Kobe 650-0047, Japan.
authors.forename: Takaya
authors.initials: T
authors.lastname: Abe
authors.affiliation: Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Developmental Biology, 2-2-3 Minatojima Minami, Chuou-ku, Kobe 650-0047, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kiyonari
authors.affiliation: 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.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kino
authors.affiliation: 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.
authors.forename: Masaru
authors.initials: M
authors.lastname: Kurosawa
authors.affiliation: Department of Neurology, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8654, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Shimizu
authors.affiliation: Laboratory for Neurogenetics, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
authors.forename: Ikuo
authors.initials: I
authors.lastname: Ogiwara
authors.affiliation: Laboratory for Neurogenetics, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yamakawa
authors.affiliation: Department of Morphological Brain Science, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Koshimizu
authors.affiliation: 1] CREST (Core Research for Evolutionary Science and Technology), JST, 7 Gobancho, Chiyoda-ku, Tokyo 102-0076, Japan [2] Department of Morphological Brain Science, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan [3] Laboratory for Neural Circuitry, Graduate School of Brain Science, Doshisha University, 4-1-1 Kizugawadai, Kizugawa-shi, Kyoto 619-0225, Japan.
authors.forename: Fumino
authors.initials: F
authors.lastname: Fujiyama
authors.affiliation: Department of Morphological Brain Science, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kaneko
authors.affiliation: RIKEN Center for Life Science Technology, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Shimizu
authors.affiliation: Department of Physiology, Hirosaki University School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori 036-8562, Japan.
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Nagatomo
authors.affiliation: Department of Physiology, Hirosaki University School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori 036-8562, Japan.
authors.forename: Katsuya
authors.initials: K
authors.lastname: Yamada
authors.affiliation: Laboratory for Molecular Mechanisms of Thalamus Development, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Shimogori
authors.affiliation: Department of Neurology, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Hattori
authors.affiliation: Neurophysiology Research Group, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo 173-0015, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Miura
authors.affiliation: 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.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Nukina
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism*; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000473:pathology; D015640:Ion Channel Gating / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D036421:Nerve Fibers, Unmyelinated / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D018408:Patch-Clamp Techniques; D034622:RNA Interference; D034741:RNA, Small Interfering; D011901:Ranvier's Nodes / Q000378:metabolism; D062585:Voltage-Gated Sodium Channel beta-4 Subunit / Q000235:genetics*
chemical_list: C506812:Htt protein, mouse; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; C497241:Scn4b protein, mouse; D062585:Voltage-Gated Sodium Channel beta-4 Subunit