| Project/Area Number |
26293056
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General pharmacology
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| Research Institution | National Institute of Health Sciences |
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Principal Investigator |
Kanda Yasunari 国立医薬品食品衛生研究所, 薬理部, 室長 (70510387)
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| Co-Investigator(Kenkyū-buntansha) |
大島 英揮 名古屋大学, 医学部附属病院, 講師 (40378188)
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| Co-Investigator(Renkei-kenkyūsha) |
Kurokawa Junko 静岡県立大学, 薬学部, 教授 (40396982)
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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 |
¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000)
Fiscal Year 2016: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2015: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
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| Keywords | iPS細胞 / 心筋細胞 / 成熟化 / インシリコ / イオンチャネル / 安全性薬理 / 不整脈 / 安全性評価 / 創薬 / ヒトiPS細胞 / 多点電極 / 興奮伝播 / 液性因子 / 心筋 / 幹細胞 / 再生医療 |
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| Outline of Final Research Achievements |
Drug-induced cardiac arrhythmias have been a major reason for drug withdrawal at late stage of clinical trials. Human induced pluripotent stem cell-derived cardiomyocytes (iPS-CMs) are expected to be applicable to cardiac drug safety testing as research tools. In the present study, our patch-clamp recordings and imaging with voltage-sensitive dye revealed that iPS-CMs exhibited relatively depolarized maximum diastolic potential and lower conduction velocity, suggesting an immature differentiation state of the iPS-CMs. We next established our mathematical simulation in iPS-CMs and found that low expression of the inward-rectifier potassium (IK1) channel is a determinant of spontaneous activity. We also fond that transduction of KCNJ2, which encodes the IK1 channel, induced electrophysiological maturation of iPS-CMs. Thus, our novel approach would provide new insights into the evaluation of drug-induced caridiac toxicities in iPS-CMs.
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