新着情報

小脳可塑性と運動学習におけるジャンクトフィリンの機能　(2007. 2)

Junctophilin-mediated channel crosstalk essential for cerebellar synaptic plasticity 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. (EMBO J. 26, 1924-1933, 2007)

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 at parallel fiber-PC synapses adversely established long-term potentiation in the JP-DKO cerebellum due primarily 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 long-term depression and motor functions.