TY - JOUR
T1 - Singular localization of sodium channel β4 subunit in unmyelinated fibres and its role in the striatum
AU - Miyazaki, Haruko
AU - Oyama, Fumitaka
AU - Inoue, Ritsuko
AU - Aosaki, Toshihiko
AU - Abe, Takaya
AU - Kiyonari, Hiroshi
AU - Kino, Yoshihiro
AU - Kurosawa, Masaru
AU - Shimizu, Jun
AU - Ogiwara, Ikuo
AU - Yamakawa, Kazuhiro
AU - Koshimizu, Yoshinori
AU - Fujiyama, Fumino
AU - Kaneko, Takeshi
AU - Shimizu, Hideaki
AU - Nagatomo, Katsuhiro
AU - Yamada, Katsuya
AU - Shimogori, Tomomi
AU - Hattori, Nobutaka
AU - Miura, Masami
AU - Nukina, Nobuyuki
N1 - Funding Information:
We thank Dr Mika Tanaka (RIKEN BSI) for supporting the generation of Scn4b-Venus transgenic mice. We thank Takumi Akagi (RIKEN BSI) for technical support and advice on EM analysis. We thank Dr Toshihiko Hosoya (RIKEN BSI) for teaching the technique of fluorescence in situ hybridization. We thank Dr Jun-ichi Miyazaki (Osaka University) for providing the CAG-Cre deleter mouse and Dr Shigeyoshi Itohara (RIKEN BSI) for providing the CAG-Cre and CAG-FLPe deleter mouse. This work was supported by a
Publisher Copyright:
© 2014 Macmillan Publishers Limited. All rights reserved.
PY - 2014/11/21
Y1 - 2014/11/21
N2 - 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.
AB - 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.
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U2 - 10.1038/ncomms6525
DO - 10.1038/ncomms6525
M3 - Article
C2 - 25413837
AN - SCOPUS:84923253163
SN - 2041-1723
VL - 5
JO - Nature Communications
JF - Nature Communications
M1 - 5525
ER -