| Project/Area Number |
26460334
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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 pharmacology
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| Research Institution | Chiba University |
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Principal Investigator |
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| Research Collaborator |
Watanabe Yasuhiro 千葉大学, 医学薬学府
Matsumoto Akio 千葉大学, 大学院医学研究院, 准教授 (60437308)
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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 |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
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| Keywords | J波症候群 / 特発性心室細動 / ATP感受性K+チャネル / Kir6.1 / 遺伝子改変動物 |
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| Outline of Final Research Achievements |
Clinical reports have indicated that the pathogenesis of J wave syndrome, which can lead to sudden cardiac death, partly associates with gain-of-function (GOF) mutation (S422L) of Kir6.1, a pore-forming subunit of ATP-sensitive K+ (KATP) channel. To test the hypothesis, we created Kir6.1 transgenic (TG) mouse strains over-expressing S422L (TGmt) or wild-type (TGWT) in cardiomyocytes and compared the cardiac electrophysiology. Although both TG mouse strains showed abnormal ECG, the density of KATP current was decreased in ventricular cells of TGmt and TGWT mice compared to ventricular cells of wild-type (WT) mice. In addition, the ATP sensitivity of single KATP channel in TGmt and TGWT ventricular cells were similar to that in WT ventricular cells.
Thus, the present study failed to support the hypothesis that the Kir6.1-S422L mutation is a direct cause of J wave syndrome.
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