Project/Area Number |
25870331
|
Research Category |
Grant-in-Aid for Young Scientists (B)
|
Allocation Type | Multi-year Fund |
Research Field |
Cardiovascular medicine
General physiology
|
Research Institution | Shiga University of Medical Science |
Principal Investigator |
|
Co-Investigator(Renkei-kenkyūsha) |
KURODA Yusuke 名古屋大学, 医学部
YUASA Shinsuke 慶應義塾大学, 医学部, 講師
|
Project Period (FY) |
2013-04-01 – 2015-03-31
|
Project Status |
Completed (Fiscal Year 2014)
|
Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
|
Keywords | 不整脈 / 分子心臓病態学 / 疾患特異的iPS細胞 / 心筋細胞 / QT延長症候群 / 生理学的機能解析 |
Outline of Final Research Achievements |
Long QT syndrome type 7 (LQT-7) is caused by a mutation in the KCNJ2 gene, and characterized by ventricular tachyarrhythmias associated with QT/QU interval prolongation, periodic paralysis and dysmorphic features. We generated induced pluripotent stem cells (iPSCs) from three LQT-7 patients carrying the KCNJ2 different mutations, and analyzed iPSC-derived cardiomyocytes (iPS-CMs).We measured action potentials in single iPS-CMs. There are no significant difference in action potential duration at 50% and 90% repolarization, and maximum diastolic potential between LQT-7 and wild type. In multi-electrode arrays analyses, flecainide reduced ectopic activities in LQT-7-derived cardiomyocytes. In condition with flecainide pre-administration, isoproterenol did not induce arrhythmic events, which suggests that flecainide has prophylactic effect in LQT-7-derived cardiomyocytes. This study suggest that iPS-CM could be a useful model for exploring disease mechanisms and drug screening.
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