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Junctophilin‐mediated channel crosstalk essential for cerebellar synaptic plasticity
Author(s) -
Kakizawa Sho,
Kishimoto Yasushi,
Hashimoto Kouichi,
Miyazaki Taisuke,
Furutani Kazuharu,
Shimizu Hidemi,
Fukaya Masahiro,
Nishi Miyuki,
Sakagami Hiroyuki,
Ikeda Atsushi,
Kondo Hisatake,
Kano Masanobu,
Watanabe Masahiko,
Iino Masamitsu,
Takeshima Hiroshi
Publication year - 2007
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601639
Subject(s) - biology , crosstalk , synaptic plasticity , neuroscience , plasticity , microbiology and biotechnology , genetics , materials science , optics , physics , receptor , composite material
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 Ca 2+ ‐induced Ca 2+ release and the subsequent opening of small‐conductance Ca 2+ ‐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 Ca 2+ ‐mediated communication between voltage‐gated Ca 2+ channels, RyRs and SK channels, which modulates the excitability of PCs and is fundamental to cerebellar LTD and motor functions.