Junctophilin-mediated channel crosstalk essential for cerebellar synaptic plasticity

Sho Kakizawa, Yasushi Kishimoto, Kouichi Hashimoto, Taisuke Miyazaki, Kazuharu Furutani, Hidemi Shimizu, Masahiro Fukaya, Miyuki Nishi, Hiroyuki Sakagami, Atsushi Ikeda, Hisatake Kondo, Masanobu Kano, Masahiko Watanabe, Masamitsu Iino, Hiroshi Takeshima

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

Functional crosstalk between cell-surface and intracellular ion channels plays important roles in excitable cells and is structurally supported by junctophilins (JPs) in muscle cells. Here, we report a novel form of channel crosstalk in cerebellar Purkinje cells (PCs). The generation of slow afterhyperpolarization (sAHP) following complex spikes in PCs required ryanodine receptor (RyR)-mediated Ca2+-induced Ca2+ release and the subsequent opening of small-conductance Ca2+-activated K+ (SK) channels in somatodendritic regions. Despite the normal expression levels of these channels, sAHP was abolished in PCs from mutant mice lacking neural JP subtypes (JP-DKO), and this defect was restored by exogenously expressing JPs or enhancing SK channel activation. The stimulation paradigm for inducing long-term depression (LTD) at parallel fiber-PC synapses adversely established long-term potentiation in the JP-DKO cerebellum, primarily due to the sAHP deficiency. Furthermore, JP-DKO mice exhibited impairments of motor coordination and learning, although normal cerebellar histology was retained. Therefore, JPs support the Ca2+-mediated communication between voltage-gated Ca2+ channels, RyRs and SK channels, which modulates the excitability of PCs and is fundamental to cerebellar LTD and motor functions.

Original languageEnglish (US)
Pages (from-to)1924-1933
Number of pages10
JournalEMBO Journal
Volume26
Issue number7
DOIs
StatePublished - Apr 4 2007
Externally publishedYes

Keywords

  • Afterhyperpolarization
  • Long-term depression
  • Purkinje cell
  • Ryanodine receptor
  • SK channel

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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  • Cite this

    Kakizawa, S., Kishimoto, Y., Hashimoto, K., Miyazaki, T., Furutani, K., Shimizu, H., Fukaya, M., Nishi, M., Sakagami, H., Ikeda, A., Kondo, H., Kano, M., Watanabe, M., Iino, M., & Takeshima, H. (2007). Junctophilin-mediated channel crosstalk essential for cerebellar synaptic plasticity. EMBO Journal, 26(7), 1924-1933. https://doi.org/10.1038/sj.emboj.7601639