Analysis of drug-induced long QT syndrome using iPS cell-derived cardiomyocytes of inherited arrhythmic patients
| Project/Area Number |
25461051
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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 |
Cardiovascular medicine
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| Research Institution | Nagoya University |
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Principal Investigator |
NIWA RYOKO 名古屋大学, 環境医学研究所, 研究員 (00216467)
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| Co-Investigator(Kenkyū-buntansha) |
神谷 香一郎 名古屋大学, 環境医学研究所, 教授 (50194973)
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| Project Period (FY) |
2013-04-01 – 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 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 遺伝性不整脈 / iPS細胞 / 薬物誘発性 / QT延長症候群 / イオンチャネル |
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| Outline of Final Research Achievements |
This study aimed to investigate cardiac pathogenesis and effective treatment in Andersen syndrome, a rare inherited channelopathy, using specific induced pluripotent stem cell (iPSC).
We reprogrammed somatic cells from three ATS patients carrying the KCNJ2 mutations to generate iPSCs. Multi-electrode arrays (MEAs) revealed strong arrhythmic events in the ATS-iPSC-derived cardiomyocytes. Using Ca2+ imaging, we found a significantly higher incidence of irregular Ca2+ release in the ATS-iPSC-derived cardiomyocytes. Flecainide, but not the sodium channel blocker, pilsicainide, suppressed these irregular Ca2+ release and arrhythmias, suggesting that the effect was not via sodium channels blocking. A reverse-mode Na+/Ca2+exchanger (NCX) inhibitor, KB-R7943, was also found to suppress the irregular Ca2+ release, and whole-cell voltage clamping of isolated guinea-pig ventricular myocytes confirmed that flecainide directly affect the NCX current.
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Report
(5 results)
Research Products
(12 results)
