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

Haruko Miyazaki, Fumitaka Oyama, Ritsuko Inoue, Toshihiko Aosaki, Takaya Abe, Hiroshi Kiyonari, Yoshihiro Kino, Masaru Kurosawa, Jun Shimizu, Ikuo Ogiwara, Kazuhiro Yamakawa, Yoshinori Koshimizu, Fumino Fujiyama, Takeshi Kaneko, Hideaki Shimizu, Katsuhiro Nagatomo, Katsuya Yamada, Tomomi Shimogori, Nobutaka Hattori, Masami MiuraNobuyuki Nukina

Research output: Contribution to journalArticlepeer-review

41 Citations (Scopus)

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.

Original languageEnglish
Article number5525
JournalNature communications
Volume5
DOIs
Publication statusPublished - Nov 21 2014
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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