| Project/Area Number |
08407002
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General physiology
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| Research Institution | NAGOYA UNIVERSITY |
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Principal Investigator |
KUBA Konji SCHOOL OF MEDICINE, NAGOYA UNIVERSITY PROFESSOR, 医学部, 教授 (60080561)
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| Co-Investigator(Kenkyū-buntansha) |
NARITA Kazuhiko School of Medicine, Kawasaki Medical College Research Associate, 医学部, 助手 (60104808)
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| Project Period (FY) |
1996 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥39,700,000 (Direct Cost: ¥39,700,000)
Fiscal Year 1999: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1998: ¥9,800,000 (Direct Cost: ¥9,800,000)
Fiscal Year 1997: ¥6,400,000 (Direct Cost: ¥6,400,000)
Fiscal Year 1996: ¥22,700,000 (Direct Cost: ¥22,700,000)
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| Keywords | Ryanodine receptor / CaィイD12+ィエD1 channel / CaィイD12+ィエD1 release / Presynaptic terminals / CaィイD12+ィエD1-dependent KィイD1+ィエD1 channel / Action potential / Transmitter exocytosis / plasticity / シナプス前経末 / ライアノジン受容体 / 短期可塑性 / Ca^<2+>誘起性Ca^<2+>遊離 / 電位依存性Ca^<2+>チャンネル / ウシガエル交感神経節細胞 / カエル運動神経終末 / 開口放出 / 同期的興奮 / 細胞内Ca^<2+> / カエル神経筋接合部 / 交感神経節細胞 / シナプス可塑性 / ニコチン性シナプス / 長期増強 / 超短パルスレーザー / 二光子励起 / レーザー顕微鏡 / ニューロン / 空間解像度 / 光軸方向解像度 / Ca^<2+>蛍光プローブ |
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| Research Abstract |
The object of this study was to clarify how intracellular CaィイD12+ィエD1 release is activated by neuron activity and regulates synaptic transmission and modulation.
At frog motor nerve terminals, CaィイD12+ィエD1 entry induced by relatively long-lasting repetitive tetani causes the activation of CaィイD12+ィエD1/calmodulin-dependent kinase II and the production of cyclic ADP-ribose, which result in the priming of the mechanism of CaィイD12+ィエD1-induced CaィイD12+ィエD1 release (CICR) via ryanodine receptors and the subsequent activation of CICR. The inactivation of this CICR mechanism is inhibited by the activation of protein kinase C. Furthermore, in bullfrog sympathetic ganglia, CaィイD12+ィエD1 entry caused by repetitive presynaptic activity primes the mechanism of CICR via IPィイD23ィエD2 receptors at the presynaptic terminals. This causes the activation of the protein synthesis-dependent mechanism of the long-term potentiation of transmitter release.
In bullfrog sympathetic ganglion cells, ryanodine recept
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ors were found to exist close to N-type voltage-gated CaィイD12+ィエD1 channels that activate the CaィイD12+ィエD1 channel and BK-type CaィイD12+ィエD1-dependent KィイD1+ィエD1 channels, thus forming a functional triad. The activation of CICR via this functional triad in the submembrane regions of a few μm shapes the spike repolarization. On the other hand, SK-type CaィイD12+ィエD1-dependent KィイD1+ィエD1 channels loosely couples with this triad, forming the slow afterhyperpolarization. The mechanism of spike repolarization wanes due to the inactivation of CICR during repetitive action potentials, while the slow afterhyperpolarization increases in time course for the increase in CaィイD12+ィエD1 entry due to the prolongation of the spike duration and the accumulation of intracellular CaィイD12+ィエD1. The network of CaィイD12+ィエD1 stores endowed with ryanodine receptors in the submembrane regions connects with the nuclear membrane envelopes and causes CaィイD12+ィエD1 release in the nucleus.
These findings suggest in general the existence of functional coupling among ryanodine receptors, CaィイD12+ィエD1 channels and CaィイD12+ィエD1-activated functional molecules in neurons, contributing to the fine regulation of CaィイD12+ィエD1-dependent physiological functions. Less
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