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 language | English (US) |
|---|---|
| Pages (from-to) | 1924-1933 |
| Number of pages | 10 |
| Journal | EMBO Journal |
| Volume | 26 |
| Issue number | 7 |
| DOIs | |
| State | Published - Apr 4 2007 |
| Externally published | Yes |
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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
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 journal › Article
}
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 -