Roles of oxygen-sensitive TRP channels in cerebral hypoxia
| Project/Area Number |
16K08494
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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 | Oita University (2017-2018)
Kyoto University (2016) |
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Principal Investigator |
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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 |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | イオンチャネル / 低酸素応答 / TRPチャネル / カルシウム / 酸素センサー |
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| Outline of Final Research Achievements |
The brain is highly vulnerable to O2 deprivation. It is understood that specialized O2-sensing elements have evolved to monitor and ensure adequate oxygenation of the arterial blood supplying the central nervous system (CNS) with O2. However, peripheral chemoreceptors are unable to directly monitor local pO2 changes, which results from variable levels of neuronal activity or blood perfusion within CNS. Here, we have found that oxygen-sensitive TRPA1 channels is activated by hypoxia in astrocytes. This induces Ca2+ influx that triggers release of ATP from astrocytes to potentiate the activity of the respiratory center. These results suggest that astrocytic TRPA1 plays a specific role in hypoxia adaption of respiratory depth.
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| Academic Significance and Societal Importance of the Research Achievements |
脳虚血とは、脳の循環血液量が減少し、機能障害を生ずる状態である。脳は虚血状態に非常に弱いことから、低酸素状態を素早く感知し虚血状態を打破するための応答が必要である。しかし、脳内における局所的な酸素分圧の感知・応答機構はまだ分かっていない。本研究では、脳内において酸素感受性イオンチャネルであるTRPA1チャネルが、酸素センサーとして働いていることを見出した。本研究の成果は、虚血性細胞障害に対する治療戦略を考える上で、標的にすべき細胞、分子を明確にすることが求められていることから、疾病の予防・治療戦略の確立にも影響を与えると予想される。
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Report
(4 results)
Research Products
(18 results)
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[Journal Article] Molecular and functional dissection of RIM protein multi-point interaction with P/Q-type Ca2+ channel CaV2.1 α1 subunits2017
Author(s)
Hirano M, Takada Y, Wong CF, Yamaguchi K, Kotani K, Kurokawa T, Mori MX, Snutch TP, Ronjat M, De Waard M, Mori Y
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Journal Title
J. Biol. Chem.
Volume: 292
Issue: 22
Pages: 1-17
DOI
Related Report
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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