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小脳プルキンエ細胞樹状突起におけるカルシウムシグナリングの解析

Research Project

Project/Area Number 15029208
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionThe University of Tokyo

Principal Investigator

井上 貴文  東京大学, 医科学研究所, 助教授 (10262081)

Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥6,600,000 (Direct Cost: ¥6,600,000)
Fiscal Year 2004: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2003: ¥3,300,000 (Direct Cost: ¥3,300,000)
Keywordsカルシウム / 小脳プルキンエ細胞 / 神経細胞 / 樹状突起 / IP3受容体 / カルシウムチャンネル
Research Abstract

細胞内Ca^<2+>放出チャンネルである1型イノシトール3リン酸受容体(IP3R1)は小脳プルキンエ細胞に非常に豊富に発現しており、ERからのCa^<2+>放出の主要な機能を担っている。プルキンエ細胞樹状突起でのCa^<2+>動態はきわめて複雑な時間,空間的特性をもっており、細胞内メカニズムを厳密かつ精妙に制御している。平行線維入力時のプルキンエ細胞樹状突起のCa^<2+>動態において、細胞外からの流入・細胞内放出機構それぞれの関与の度合いを詳細に検討した。50Hz、3〜8発の刺激で見られるCa^<2+>の流入と細胞内からの放出による二相性のCa^<2+>上昇は、刺激回数を増加すると一相性となり、持続時間は刺激回数に比例し、50発刺激ではCa^<2+>上昇は6〜8秒程度持続し、Ca^<2+>濃度は200μMにまで上昇していると推定された。この大きなCa^<2+>上昇はほとんどがCa^<2+>流入によるものであり、更にNa^+濃度とCa^<2+>濃度変化を比較した結果、P型Caチャンネルを通ったCa^<2+>がその本態であることを明らかにした(Kuruma et al.,2003)。
更に小脳皮質の生後発達に伴うCa^<2+>放出活性の変化を検討するため、異なる日齢のマウスを用いて二相性Ca^<2+>上昇を観察した。2〜3週齢のマウスのプルキンエ細胞ではCa^<2+>放出が相対的に大きく、4週齢以降では逆にCa^<2+>流入の方が大きかった。すなわち平行線維刺激で誘起されるプルキンエ細胞樹状突起のCa^<2+>動態は2週前後の幼弱なマウスにおいてはCa^<2+>放出がCa^<2+>流入よりも支配的であり、成長に伴ってそれが逆転することが示された。2週と4週齢のマウスを用いて平行線維・プルキンエ細胞シナプスのLTDの起こりやすさの差異を検討した。2週齢では平行線維刺激のみでLTDを起こす場合が見られ、同時に測定したCa^<2+>放出活性の大きさとLTDの度合いに相関が見られた。同じ刺激方法では4週齢ではLTDは見られなかった(投稿準備中)。以上の結果から、小脳皮質が発達・成熟をする2週齢前後では、シナプス結合の可塑的変化や成熟化にシナプス後部のCa^<2+>放出能が重要な役割を果たしているという結論に至った。

Report

(2 results)
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (23 results)

All 2005 2004 Other

All Journal Article (12 results) Publications (11 results)

  • [Journal Article] Na^+/K^+ ATPase and its functional couplings with Na^+/Ca^<2+> exchangers in mouse embryonic stem cells during differentiation into cardiomyocytes.2005

    • Author(s)
      Keishi Otsu
    • Journal Title

      Cell Calcium 37

      Pages: 137-151

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Cluster formation of inositol 1,4,5-trisphosphate receptor requires its transition to open state.2005

    • Author(s)
      Yoko Tateishi
    • Journal Title

      The Journal of Biological Chemistry in press

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Molecular cloning of mouse type 2 and type 3 inositol 1,4,5-trisphosphate receptors and identification of a novel type 2 receptor splice variant.2005

    • Author(s)
      Miwako Iwai
    • Journal Title

      The Journal of Biological Chemistry in press

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Lateral diffusion of inositol 1,4,5-trisphosphate receptor type 1 is regulated by actin filaments and 4.1N in neuronal dendrites.2004

    • Author(s)
      Kazumi Fukatsu
    • Journal Title

      The Journal of Biological Chemistry 279

      Pages: 48976-48982

    • Related Report
      2004 Annual Research Report
  • [Journal Article] An RNA-interacting protein SYNCRIP (heterogeneous nuclear ribonuclear protein Q1/NSAP1) is a component of mRNA granule transported with inositol 1,4,5-trisphosphate receptor type 1 mRNA in neuronal dendrites.2004

    • Author(s)
      Hiroko Bannai
    • Journal Title

      The Journal of Biological Chemistry 279

      Pages: 53427-53434

    • Related Report
      2004 Annual Research Report
  • [Journal Article] The kinetic profile of intracellular calcium predicts long-term potentiation and long-term depression.2004

    • Author(s)
      Iskandar Ismailov
    • Journal Title

      The Journal of Neuroscience 24

      Pages: 9847-9861

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Hypocretin/Orexin peptide signaling in the ascending arousal system : Elevation of intracellular calcium in the mouse dorsal raphe and laterodorsal tegmentum.2004

    • Author(s)
      Kristi A.Kohlmeier
    • Journal Title

      Journal of Neurophysiology 92

      Pages: 221-235

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Activity-dependent expression of inositol 1,4,5-trisphosphate receptor type 1 in hippocampal neurons.2004

    • Author(s)
      Weihua Cai
    • Journal Title

      The Journal of Biological Chemistry 279

      Pages: 23691-23698

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Kinesin dependent, rapid, bidirectional transport of inositol-1,4,5-trisphosphate receptor containing particles in the dendrite of hippocampal neurons.2004

    • Author(s)
      Hiroko Bannai
    • Journal Title

      Journal of Cell Science 117

      Pages: 163-175

    • Related Report
      2004 Annual Research Report
  • [Journal Article] The regulatory domain of the inositol 1,4,5-trisphosphate receptor is necessary to keep the channel domain closed : Possible physiological significance of specific cleavage bycaspase 3.2004

    • Author(s)
      Tomohiro Nakayama
    • Journal Title

      Biochemical Journal 377

      Pages: 299-307

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Distinct roles of inositol 1,4,5-trisphosphate receptor types 1 and 3 in Ca^<2+> signaling.2004

    • Author(s)
      Mitsuharu Hattori
    • Journal Title

      The Journal of Biological Chemistry 279

      Pages: 11967-11975

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Regulation of TRPC6 channel activity by tyrosine phosphorylation.2004

    • Author(s)
      Chihiro Hisatsune
    • Journal Title

      The Journal of Biological Chemistry 279

      Pages: 18887-18894

    • Related Report
      2004 Annual Research Report
  • [Publications] Kristi A.Kohlmeier: "Hypocretin/Orexin peptide signaling in the ascending arousal system: Regulation of intracellular calcium in the dorsal raphe and laterodorsal tegmentum."Journal of Neurophysiology. in press.

    • Related Report
      2003 Annual Research Report
  • [Publications] Weihua Cai: "Activity-dependent expression of the type 1 inositol 1,4,5-trisphosphate receptor type 1 in hippocampal neurons."The Journal of Biological Chemistry. in press.

    • Related Report
      2003 Annual Research Report
  • [Publications] Chihiro Hisatsune: "Regulation of TRPC6 channel activity by tyrosine phosphorylation."The Journal of Biological Chemistry. in press.

    • Related Report
      2003 Annual Research Report
  • [Publications] Mitsuharu Hattori: "Distinct roles of inositol 1,4,5-trisphosphate receptor type 1 and type 3 in Ca^<2+> signaling."The Journal of Biological Chemistry. in press.

    • Related Report
      2003 Annual Research Report
  • [Publications] Tomohiro Nakayama: "The regulatory domain of the inositol 1,4,5-trisphosphate receptor is necessary to keep the channel domain closed: Possible physiological significance of specific cleavage bycaspase 3."Biochemical Journal. 377. 299-307 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hiroko Bannai: "Kinesin dependent, rapid, bidirectional transport of inositol- 1,4,5-trisphosphate receptor containing particles in the dendrite of hippocampal neurons."Journal of Cell Science. 117. 163-175 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Akinori Kuruma: "Dynamics of Ca^<2+> Na^+ in the dendrite of mouse cerebellar Purkinje cells evoked by parallel fiber stimulation."European Journal of Neuroscience. 18. 2677-2689 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kiyoko Fukami: "Phospholipase Cδ4 is required for Ca^<2+>-mobilization essential for acrosome reaction in sperm."The Journal of Cell Biology. 161. 79-88 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yukinori Minoshima: "Phosphorylation by Aurora B converts MgcRacGAP to a RhoGAP during cytokinesis."Developmental Cell. 4. 549-560 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] T.Nagase: "Long-term potentiation and long-term depression in hippocampa 1 CA1 neurons of mice lacking the IP3 type 1 receptor."Neuroscience. 117. 821-830 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hiroki Yasuda: "Imaging of calcineurin activated by long-term depression-inducing synaptic inputs in living neurons of rat visual cortex."European Journal of Neuroscience. 17. 287-297 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2018-03-28  

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