title: Junctophilin-mediated channel crosstalk essential for cerebellar synaptic plasticity.
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 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.
authors.affiliation: Department of Pharmacology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Sho
authors.initials: S
authors.lastname: Kakizawa
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kishimoto
authors.forename: Kouichi
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Taisuke
authors.initials: T
authors.lastname: Miyazaki
authors.forename: Kazuharu
authors.initials: K
authors.lastname: Furutani
authors.forename: Hidemi
authors.initials: H
authors.lastname: Shimizu
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fukaya
authors.forename: Miyuki
authors.initials: M
authors.lastname: Nishi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sakagami
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ikeda
authors.forename: Hisatake
authors.initials: H
authors.lastname: Kondo
authors.forename: Masanobu
authors.initials: M
authors.lastname: Kano
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Iino
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takeshima
mesh_terms: D000200:Action Potentials; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015640:Ion Channel Gating; D007858:Learning; D036881:Long-Term Synaptic Depression; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009048:Motor Skills / Q000502:physiology; D009473:Neuronal Plasticity; D011689:Purkinje Cells / Q000166:cytology* / Q000378:metabolism*; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism*; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D019837:Ryanodine Receptor Calcium Release Channel; D051640:Small-Conductance Calcium-Activated Potassium Channels; C412507:junctophilin; D002118:Calcium