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

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  • Haruko Miyazaki

    (Juntendo University Graduate School of Medicine
    Laboratory for Structural Neuropathology, RIKEN Brain Science Institute
    Laboratory for Molecular Mechanisms of Thalamus Development, RIKEN Brain Science Institute
    CREST (Core Research for Evolutionary Science and Technology), JST)

  • Fumitaka Oyama

    (Laboratory for Structural Neuropathology, RIKEN Brain Science Institute
    Kogakuin University)

  • Ritsuko Inoue

    (Neurophysiology Research Group, Tokyo Metropolitan Institute of Gerontology)

  • Toshihiko Aosaki

    (Neurophysiology Research Group, Tokyo Metropolitan Institute of Gerontology)

  • Takaya Abe

    (Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Developmental Biology)

  • Hiroshi Kiyonari

    (Laboratory for Animal Resources and Genetic Engineering, RIKEN Center for Developmental Biology)

  • Yoshihiro Kino

    (Juntendo University Graduate School of Medicine
    Laboratory for Structural Neuropathology, RIKEN Brain Science Institute
    Laboratory for Molecular Mechanisms of Thalamus Development, RIKEN Brain Science Institute
    CREST (Core Research for Evolutionary Science and Technology), JST)

  • Masaru Kurosawa

    (Juntendo University Graduate School of Medicine
    Laboratory for Structural Neuropathology, RIKEN Brain Science Institute
    Laboratory for Molecular Mechanisms of Thalamus Development, RIKEN Brain Science Institute
    CREST (Core Research for Evolutionary Science and Technology), JST)

  • Jun Shimizu

    (University of Tokyo)

  • Ikuo Ogiwara

    (Laboratory for Neurogenetics, RIKEN Brain Science Institute)

  • Kazuhiro Yamakawa

    (Laboratory for Neurogenetics, RIKEN Brain Science Institute)

  • Yoshinori Koshimizu

    (Graduate School of Medicine, Kyoto University)

  • Fumino Fujiyama

    (CREST (Core Research for Evolutionary Science and Technology), JST
    Graduate School of Medicine, Kyoto University
    Laboratory for Neural Circuitry, Graduate School of Brain Science, Doshisha University)

  • Takeshi Kaneko

    (Graduate School of Medicine, Kyoto University)

  • Hideaki Shimizu

    (RIKEN Center for Life Science Technology)

  • Katsuhiro Nagatomo

    (Hirosaki University School of Medicine)

  • Katsuya Yamada

    (Hirosaki University School of Medicine)

  • Tomomi Shimogori

    (Laboratory for Molecular Mechanisms of Thalamus Development, RIKEN Brain Science Institute)

  • Nobutaka Hattori

    (Juntendo University Graduate School of Medicine)

  • Masami Miura

    (Neurophysiology Research Group, Tokyo Metropolitan Institute of Gerontology)

  • Nobuyuki Nukina

    (Juntendo University Graduate School of Medicine
    Laboratory for Structural Neuropathology, RIKEN Brain Science Institute
    Laboratory for Molecular Mechanisms of Thalamus Development, RIKEN Brain Science Institute
    CREST (Core Research for Evolutionary Science and Technology), JST)

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.

Suggested Citation

  • Haruko Miyazaki & Fumitaka Oyama & Ritsuko Inoue & Toshihiko Aosaki & Takaya Abe & Hiroshi Kiyonari & Yoshihiro Kino & Masaru Kurosawa & Jun Shimizu & Ikuo Ogiwara & Kazuhiro Yamakawa & Yoshinori Kosh, 2014. "Singular localization of sodium channel β4 subunit in unmyelinated fibres and its role in the striatum," Nature Communications, Nature, vol. 5(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6525
    DOI: 10.1038/ncomms6525
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