Contribution of spacio-temporal Ca2+ dynamics to the pacemaker rhythm in sinoatrial node cells
| Project/Area Number |
16K18996
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
General physiology
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| Research Institution | Ritsumeikan University |
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Principal Investigator |
Himeno Yukiko 立命館大学, 生命科学部, 助教 (10534365)
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| Research Collaborator |
Noma Akinori
Amano Akira
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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 |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 洞房結節 / 細胞内Ca2+ / 歩調取り / コンピュータシミュレーション / T型Caチャネル / L型Caチャネル / Ca2+放出ユニット / LCC-RyR共役モデル / 自動能 / Caオシレーション / シミュレーション / 洞房結節細胞 / 心房細胞 / 心室細胞 / iPS心筋細胞 / 生理学 / 生体シミュレーション / Ca2+ |
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| Outline of Final Research Achievements |
To evaluate the contribution of intracellular Ca<SUP>2+</SUP> dynamics to the pacing mechanism of the sinus node (SAN) pacemaker cells, an SAN simulation model was developed. The model introduced a framework to calculate local Ca<SUP>2+</SUP> concentration (Hinch model Biophys J, Hinch 2004), which was firstly introduced in a ventricular myocyte model (HuVEC model Biophys J, Himeno et al. 2015). As a result, it was suggested that contribution of NaCa exchanger activated by extremely high local Ca<SUP>2+</SUP> concentration was not small despite the cell membrane and the sarcoplasmic reticulum membrane were more weakly coupled and the number of Ca<SUP>2+</SUP> releasing units was smaller in SAN cells compared to ventricular myocytes.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究成果は、細胞内Ca<SUP>2+</SUP>動態を、数理時空間上でこれまでよりも高い精度で再現し、実験で入手可能なデータと摺り合わせを行っていくためのプラットフォームを提案することができた。これにより、さらに現実的なモデルへと精緻化を進めていくためには、実験でどのようなデータを計測してどのパラメータへと反映させていくべきかというような方策も立てることができるようになった点は意義深い。特に、面積や体積を見積もるための細胞内部構造や拡散定数など、Ca<SUP>2+</SUP>濃度計算に関わる部分に関連する計測技術の発展により、精度は格段に向上するだろう。
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Report
(4 results)
Research Products
(48 results)
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[Presentation] Significance of cell-specific precise computer simulation using new mathematical models of human induced pluripotent stem cell derived cardiomyocyte in drug testing.2018
Author(s)
Hirohiko Kohjitani, Shigeya Kouda, Yukiko Himeno, Takeru Makiyama, Fumika Yokoi, Sayako Hirose, Yimin Wuriyanghai, Yuta Yamamoto, Minoru Horie, Takeshi Kimura, Akinori Noma, Akira Amano.
Organizer
European Society of Cardiology Congress 2018 (ESC2018)
Related Report
Int'l Joint Research
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[Presentation] Mathematical modeling and analysis of electrophysiological characteristics of the ventricular, atrial, and nodal-like hiPSC-CMs2017
Author(s)
Hirohiko Kohjitani, Shigeya Kouda, Yukiko Himeno, Natsuki Yamamoto, Takeru Makiyama, Takeshi Harita, Takeshi Kimura, Akinori Noma, Akira Amano
Organizer
第94回日本生理学会大会
Place of Presentation
アクトシティ浜松（静岡県浜松市）
Year and Date
2017-03-29
Related Report
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