Molecular Mechanisms of Atrial Fibrillation Suppression by Leak K+ Current
| Project/Area Number |
20K16116
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 48020:Physiology-related
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| Research Institution | Akita University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2022: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 心房性不整脈 / リークK電流 / ノックアウトマウス / リークKチャネル / 細胞骨格 / 不整脈 / 分子間相互作用 / 遺伝子改変マウス / 心房細動 / K+チャネル |
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| Outline of Research at the Start |
下記（１）→（４）へと順次研究を進めていく．
（１）ラット病態モデルを用いたリークK+電流の電気生理学的・分子生物学的研究．
（２）培養細胞を用いたリークK+チャネルの分子制御機構の解明．
（３）遺伝子改変動物を用いたリークK+チャネルの病態生理学的意義の確認．
（４）ヒトサンプルを用いた病態生理・治療法開拓研究への応用．
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| Outline of Final Research Achievements |
In a rat model of induced atrial arrhythmias, activation of leaky K currents suppresses arrhythmias. In conditioned knockout (CKO) mice of the leaky K channel, atrial arrhythmias were observed to be prolonged by sympathetic nerve stimulation. We are currently examining the membrane potential stabilizing effects of leaky K channels at the cellular level.
We have also identified a novel molecule that interacts with leaky K channels. To generate CKO of this molecule, we obtained floxed and Cre mice. This CKO is expected to indirectly affect the leaky K current, but this has not yet been tested.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は心房筋の膜電位の安定に、心室筋細胞とは違う機構が存在する可能性を示唆している。心室筋では強力に膜電位を固定している内向き整流性K電流があるが、心房筋ではこの電流は比較的小さい。一方で、リークK電流を活性化すると不整脈が抑制され、ノックアウトすると不整脈が増える事実は、心臓生理学に新しい知見をもたらす可能性がある。また、上室性不整脈に対するリークK電流の影響は明らかなため、病態生理学的、あるいは新規抗不整脈薬の開拓にも意義があるものと思われる。
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Report
(4 results)
Research Products
(14 results)
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[Journal Article] Comparative Study of Transcriptome in the Hearts Isolated from Mice, Rats, and Humans2022
Author(s)
Okada D, Okamoto Y, Io T, Oka M, Kobayashi D, Ito S, Yamada R, Ishii K, Ono K.
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Journal Title
Biomolecules
Volume: 12
Issue: 6
Pages: 859-876
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Small-volume vitrification and rapid warming yield high survivals of one-cell rat embryos in cryotubes2021
Author(s)
Fukuda Y, Higashiya M, Obata T, Basaki K, Yano M, Matsumura K, Ono K, Ohba T, Okamoto Y, Nishijima K, Seki S
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Journal Title
Biol Reprod
Volume: ioab059
Issue: 1
Pages: 258-266
DOI
Related Report
Peer Reviewed / Open Access
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