2003 Fiscal Year Annual Research Report

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 Institution	The University of Tokyo
Principal Investigator	井上貴文東京大学, 医科学研究所, 助教授 (10262081)
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週齢から4週齢は小脳皮質が発達・成熟を遂げる時期であり、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+>放出能が関与している可能性を示唆する。

Research Products

(11 results)

All Other

All Publications (11 results)

[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.
[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.
[Publications] Chihiro Hisatsune: "Regulation of TRPC6 channel activity by tyrosine phosphorylation."The Journal of Biological Chemistry. in press.
[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.
[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)
[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)
[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)
[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)
[Publications] Yukinori Minoshima: "Phosphorylation by Aurora B converts MgcRacGAP to a RhoGAP during cytokinesis."Developmental Cell. 4. 549-560 (2003)
[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)
[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)

2003 Fiscal Year Annual Research Report

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

Principal Investigator

井上 貴文 東京大学, 医科学研究所, 助教授 (10262081)

Research Products

[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.

[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.

[Publications] Chihiro Hisatsune: "Regulation of TRPC6 channel activity by tyrosine phosphorylation."The Journal of Biological Chemistry. in press.

[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.

[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)

[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)

[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)

[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)

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

[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)

[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)

井上貴文東京大学, 医科学研究所, 助教授 (10262081)