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Modeling and analyzing of long QT syndrome using disease-specific iPS cells

Research Project

Project/Area Number 25870331
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Cardiovascular medicine
General physiology
Research InstitutionShiga University of Medical Science

Principal Investigator

HATTORI Tetsuhisa  滋賀医科大学, 医学部, 助教 (80638932)

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.

Report

(3 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (3 results)

All 2015 2014

All Presentation (3 results)

  • [Presentation] Disease Modeling of Long-QT Syndrome Type 7 Using Patient-specific iPS Cells2015

    • Author(s)
      Yusuke Kuroda
    • Organizer
      第79回日本循環器学会学術集会
    • Place of Presentation
      osaka
    • Year and Date
      2015-04-24 – 2015-04-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] Reverse-mode Na+/Ca2+ Exchanger Inhibitor Suppresses an Arrhythmogenic Substrate in Andersen-Tawil Syndrome-induced Pluripotent Stem Cell-derived Cardiomyocytes2014

    • Author(s)
      黒田 裕介
    • Organizer
      Reverse-mode Na+/Ca2+ Exchanger Inhibitor Suppresses an Arrhythmogenic Substrate in Andersen-Tawil Syndrome-induced Pluripotent Stem Cell-derived Cardiomyocytes
    • Place of Presentation
      仙台
    • Year and Date
      2014-09-26 – 2014-09-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] Disease Modeling for Andersen-Tawil Syndrome Using Patient-Specific iPS Cell2014

    • Author(s)
      Yusuke Kuroda
    • Organizer
      第78回日本循環器学会学術集会
    • Place of Presentation
      Tokyo
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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