Article
- The EMBO Journal (2007) 26, 1924 - 1933
- doi:10.1038/sj.emboj.7601639
Published online: 8 March 2007
Subject Categories:
Junctophilin-mediated channel crosstalk essential for cerebellar synaptic plasticity
Sho Kakizawa1, Yasushi Kishimoto2, Kouichi Hashimoto2,3, Taisuke Miyazaki3, Kazuharu Furutani1, Hidemi Shimizu4, Masahiro Fukaya4, Miyuki Nishi5, Hiroyuki Sakagami6, Atsushi Ikeda5, Hisatake Kondo6, Masanobu Kano2, Masahiko Watanabe4, Masamitsu Iino1 and Hiroshi Takeshima5
- Department of Pharmacology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
- Department of Cellular Neuroscience, Graduate School of Medicine, Osaka University, Osaka, Japan
- Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Sapporo, Japan
- Department of Anatomy, Hokkaido University Graduate School of Medicine, Sapporo, Japan
- Department of Biological Chemistry, Kyoto University Graduate School of Pharmaceutical Sciences, Kyoto, Japan
- Department of Cell Biology, Tohoku University Graduate School of Medicine, Sendai, Japan
Correspondence to:
Hiroshi Takeshima, Department of Biological Chemistry, Kyoto University Graduate School of Pharmaceutical Sciences, Kyoto 606-8501, Japan. Tel.: +81 75 753 4572; Fax: +81 75 753 4605; E-mail: takeshim@pharm.kyoto-u.ac.jp
Received 2 August 2006; Accepted 8 February 2007
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.
Keywords:
- afterhyperpolarization,
- long-term depression,
- Purkinje cell,
- ryanodine receptor,
- SK channel
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