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

38 Citations (Scopus)

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

Fingerprint

Neuronal Plasticity
Crosstalk
Plasticity
Purkinje Cells
Depression
Calcium-Activated Potassium Channels
Ryanodine Receptor Calcium Release Channel
Histology
Long-Term Potentiation
Ataxia
junctophilin
Ion Channels
Synapses
Cerebellum
Muscle Cells
Muscle
Chemical activation
Communication
Cells
Learning

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)

Cite this

Kakizawa, S., Kishimoto, Y., Hashimoto, K., Miyazaki, T., Furutani, K., Shimizu, H., ... 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

Junctophilin-mediated channel crosstalk essential for cerebellar synaptic plasticity. / 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.

In: EMBO Journal, Vol. 26, No. 7, 04.04.2007, p. 1924-1933.

Research output: Contribution to journalArticle

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, vol. 26, no. 7, pp. 1924-1933. https://doi.org/10.1038/sj.emboj.7601639
Kakizawa S, Kishimoto Y, Hashimoto K, Miyazaki T, Furutani K, Shimizu H et al. Junctophilin-mediated channel crosstalk essential for cerebellar synaptic plasticity. EMBO Journal. 2007 Apr 4;26(7):1924-1933. https://doi.org/10.1038/sj.emboj.7601639
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. / Junctophilin-mediated channel crosstalk essential for cerebellar synaptic plasticity. In: EMBO Journal. 2007 ; Vol. 26, No. 7. pp. 1924-1933.
@article{610c4c22762545759523e13f8b2b69f7,
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 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",
author = "Sho Kakizawa and Yasushi Kishimoto and Kouichi Hashimoto and Taisuke Miyazaki and Kazuharu Furutani and Hidemi Shimizu and Masahiro Fukaya and Miyuki Nishi and Hiroyuki Sakagami and Atsushi Ikeda and Hisatake Kondo and Masanobu Kano and Masahiko Watanabe and Masamitsu Iino and Hiroshi Takeshima",
year = "2007",
month = "4",
day = "4",
doi = "10.1038/sj.emboj.7601639",
language = "English (US)",
volume = "26",
pages = "1924--1933",
journal = "EMBO Journal",
issn = "0261-4189",
publisher = "Nature Publishing Group",
number = "7",

}

TY - JOUR

T1 - Junctophilin-mediated channel crosstalk essential for cerebellar synaptic plasticity

AU - Kakizawa, Sho

AU - Kishimoto, Yasushi

AU - Hashimoto, Kouichi

AU - Miyazaki, Taisuke

AU - Furutani, Kazuharu

AU - Shimizu, Hidemi

AU - Fukaya, Masahiro

AU - Nishi, Miyuki

AU - Sakagami, Hiroyuki

AU - Ikeda, Atsushi

AU - Kondo, Hisatake

AU - Kano, Masanobu

AU - Watanabe, Masahiko

AU - Iino, Masamitsu

AU - Takeshima, Hiroshi

PY - 2007/4/4

Y1 - 2007/4/4

N2 - 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.

AB - 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.

KW - Afterhyperpolarization

KW - Long-term depression

KW - Purkinje cell

KW - Ryanodine receptor

KW - SK channel

UR - http://www.scopus.com/inward/record.url?scp=34247210841&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34247210841&partnerID=8YFLogxK

U2 - 10.1038/sj.emboj.7601639

DO - 10.1038/sj.emboj.7601639

M3 - Article

VL - 26

SP - 1924

EP - 1933

JO - EMBO Journal

JF - EMBO Journal

SN - 0261-4189

IS - 7

ER -