| Project/Area Number |
26460303
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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 | Kanazawa Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
芝本 利重 金沢医科大学, 医学部, 教授 (90178921)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
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| Keywords | cardiac pacemaker / mathematical model / bifurcation analysis / computer simulation / システム生理学 / 非線形力学 / 分岐理論 / 生物・生体工学 / 生物物理 / バイオペースメーカー / ヒトES細胞 / HCN4 / 数理モデル / コンピュータシミュレーション |
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| Outline of Final Research Achievements |
We have developed mathematical models for ES/iPS cell-derived cardiomyocytes as modified versions of the human ventricular and atrial myocyte models. By bifurcation analyses for the model cells, we have found that automaticity of sinoatrial node cell-like pacemaker cells is attributable to the destabilization of the equilibrium point (EP) via L-type Ca channel currents, whereas cessation of pacemaker activity of atrial or ventricular cell-like cardiomyocytes is due to the emergence of a stable EP via increase of inward-rectifier K channel currents. We further developed a multi-cellular model composed of pacemaker cells and atrial/ventricular cells, and examined functions of the pacemaker cell as a biological pacemaker. Incorporating pacemaker currents into the pacemaker cell altered functions of the biological pacemaker in the multicellular model. Incorporation of the sustained inward current was found to be most effective in the enhancement of biological pacemaker functions.
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