| Project/Area Number |
16K08513
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General physiology
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| Research Institution | National Institute of Health Sciences |
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Principal Investigator |
Tomohiko Irie 国立医薬品食品衛生研究所, 薬理部, 主任研究官 (20546551)
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| Co-Investigator(Kenkyū-buntansha) |
伊藤 哲史 金沢医科大学, 医学部, 准教授 (90334812)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | リアノジン受容体 / CICR / BKチャネル / バースト発火 / CB1 / DSE / eCB / Ca2+誘発性Ca2+放出 |
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| Outline of Final Research Achievements |
Action potentials clustered into high-frequency bursts play distinct roles in neural computations. However, little is known about ionic currents that control the duration and probability of these bursts. We found that, in cartwheel inhibitory interneurons of the dorsal cochlear nucleus, the likelihood of bursts and the interval between their spikelets were controlled by Ca2+ acting across two nanodomains, one between plasma membrane P/Q Ca2+ channels and ER ryanodine receptors and another between ryanodine receptors and large-conductance, voltage- and Ca2+-activated K+ (BK) channels. Each spike triggered CICR from the ER immediately beneath somatic, but not axonal or dendritic, plasma membrane. Moreover, immunolabeling demonstrated close apposition of ryanodine receptors and BK channels. Double-nanodomain coupling between somatic plasma membrane and hypolemmal ER cisterns provides a unique mechanism for rapid control of action potentials on the millisecond timescale.
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| Academic Significance and Societal Importance of the Research Achievements |
複数の活動電位が高頻度で発火する現象はバースト発火とよばれ，ニューロンにおける情報処理において重要な役割を果たすが，これを制御する電流については解明されていない．本研究で聴覚系の抑制性神経細胞で，バースト発火の頻度は二重のCa2+ナノドメインにおけるCa2+シグナル伝達により制御されることを見い出した．二重のナノドメインは，細胞膜のCavチャネルと小胞体膜のリアノジン受容体とのあいだ，および，リアノジン受容体と細胞膜のBKチャネルのあいだに形成されていた．活動電位にともなう脱分極によりCavチャネルが活性化し，これにより流入するCa2+がCa2+誘発性Ca2+放出を起こす事がわかった．
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