Ischemic postconditioning induced by opening of mK+ ATP channels and NMDAR silencing by mPTP opening
| Project/Area Number |
16K10735
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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 |
Neurosurgery
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| Research Institution | Nara Medical University |
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Principal Investigator |
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| Research Collaborator |
Furuta Takanori
Ogawa Yoichi
Saito Yasuhiko
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 虚血耐性現象 / ミトコンドリア / ATP依存性カリウムチャンネル / 虚血再灌流障害 / MKATPチャンネル / postconditioning / パッチクランプ法 / NMDA受容体 / 脳虚血 / 脳血管障害学 |
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| Outline of Final Research Achievements |
In the present study, we examine the precise mechanisms of IPoC using electrophysiological approach. NMDARs and anoxia mediated increase in Ca2+ were silenced during IPoC and mK+ ATP channel opener diazoxide prevented the anoxia-mediated increase in Ca2+ and reduction in NMDAR currents, however, the mPTP blocker cyclosporine A prevented the IPoC effect that NMDAR currents reduced. Furthermore, Φm depolarization was induced by the activation of mK+ ATP channels during IPoC. The present study indicates that mitochondria plays a pivotal role for neuroprotection of IPoC induced by opening of mK+ ATP channels through NMDAR silencing by mild mPTP opening.
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| Academic Significance and Societal Importance of the Research Achievements |
神経細胞の虚血耐性現象に関する報告は数多くされているが、電気生理学的側面からの報告は少ない。本研究の結果としてミトコンドリア局在KATPチャンネルの開口によってミトコンドリア内膜の脱分極が生じ、ミトコンドリアPTPから特異的にCa2+が細胞内に放出され、これが細胞膜NMDA受容体をdown-regulationさせ、このことがEPSCの低下をもたらす結果が得られた。本機序の解明が進み、今後トランスレーショナルリサーチに発展することにより、将来的には本チャンネル開口薬が脳梗塞急性期の“治療薬”として臨床応用されれば今後の脳血管障害の治療に貢献するところは大きいと考えられる。
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Report
(4 results)
Research Products
(8 results)
