| Project/Area Number |
17K08537
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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 | Shiga University of Medical Science |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
松浦 博 滋賀医科大学, 医学部, 理事 (60238962)
林 維光 滋賀医科大学, 医学部, 助教 (80242973)
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 心臓 / イオンチャネル / 心筋 / パッチクランプ / 洞房結節細胞 / イオン透過性 / ペースメーカー細胞 / 細胞内カルシウム / ペースメーカー活動 / 生理学 |
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| Outline of Final Research Achievements |
We have recently reported that L-type CaV1.3 Ca2+ channels are required for the generation of a dihydropyridine-sensitive Na+ current, previously described as the sustained inward current, Ist, in heart pacemaker cells. However, currently available recombinant CaV1.3 channels are highly selective for Ca2+ and it remains a challenge to elucidate the molecular mechanism allowing Cav1.3 channels to generate a Na+ conductance. In the present study, we show that Ist is inhibited by 9-phenathrol and flufenamic acid, both are known to block TRPM4 Ca2+-activated cation channels. In addition, simultaneous measurements of whole-cell membrane currents and intracellular Ca2+ revealed that Ist activation was accompanied by a sustained elevation of intracellular Ca2+. However, patch-clamp measurements of Ist were not affected by TRPM4 gene ablation. In conclusion, we failed to provide the evidence for the potential link between TRPM4 and Ist.
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| Academic Significance and Societal Importance of the Research Achievements |
持続性内向きNa電流（Ist）は心拍リズムの調整に強く関わることが示唆されており、その分子機構の解明は心臓の拍動リズムの仕組みという根源的な問いにも触れる生理学的に重要な課題である。本研究は、持続性内向きNa電流（Ist）の分子機構としてひとつのもっともらしい可能性を検証する試みである。結果として当該仮説は否定されたが、Istの分子機構の全容解明に向けて着実な一歩となる。重症心不全や心房細動といった心臓疾患ではリズムコントロールが重要である。Istの分子機構の解明は創薬への可能性を開き、臨床に還元され得る展開が期待される。
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