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Analysis of drug-induced hereditary long QT syndrome using induced pluripotent stem cells from patients with hereditary long QT syndrome

Research Project

Project/Area Number 22590779
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionNagoya University

Principal Investigator

NIWA Ryoko  名古屋大学, 環境医学研究所, 研究員 (00216467)

Co-Investigator(Kenkyū-buntansha) KAMIYA Kaichiro  名古屋大学, 環境医学研究所, 教授 (50194973)
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords薬剤誘発性 / QT延長症候群 / イオンチャネル / iPS細胞 / 薬物誘発性
Research Abstract

This study thus sought to better characterize ion channel cardiac disorders in Long QT Syndrome (LQT) using induced pluripotent stem cells (iPSCs). We reprogrammed somatic cells from a patient with sporadic LQTS and from controls, and differentiated them into cardiomyocytes through embryoid body (EB) formation. Electrophysiological analysis of the LQTS-iPSC-derived EBs using a multi-electrode array (MEA) system revealed a markedly prolonged field potential duration (FPD). The IKr blocker E4031 significantly prolonged FPD in control- and LQTS-iPSC-derived EBs and induced frequent severe arrhythmia only in LQTS-iPSC-derived EBs. The IKs blocker chromanol 293B did not prolong FPD in the LQTS-iPSC-derived EBs, but significantly prolonged FPD in the control EBs, suggesting the involvement of IKs disturbance in the patient. This study demonstrated that iPSCs could be useful to characterize LQTS disease as well as drug responses in the LQTS patient with a novel mutation.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (23 results)

All 2013 2012 2011 2010 Other

All Journal Article (4 results) (of which Peer Reviewed: 3 results) Presentation (19 results) (of which Invited: 1 results)

  • [Journal Article] Atrial electivity in Na+ channel blockade by acute amiodarone2013

    • Author(s)
      Suzuki T, Morishima M, Kato S, Ueda N, Honjo H, Kamiya K
    • Journal Title

      Cardiovasc Res

      Volume: 98 Issue: 1 Pages: 136-144

    • DOI

      10.1093/cvr/cvt007

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Single csystem for multi-wavelength fluorescent imaging in the heart2012

    • Author(s)
      Yamanaka Takeshi他
    • Journal Title

      CoProc IEEE Eng Med Biol S

      Volume: 2012 Pages: 3716-3719

    • DOI

      10.1109/embc.2012.6346774

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Disease characterization using LQTS-specific induced pluripotent stem cells.2012

    • Author(s)
      Egashira T, Yuasa S, Suzuki T, Tohyama S, et al.
    • Journal Title

      Cardiovasc. Res.

      Volume: 95 Issue: 4 Pages: 419-29

    • DOI

      10.1093/cvr/cvs206

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Image registration for simultaneous membrane potential and intracellular calcium in rabbit hearts.2011

    • Author(s)
      Hernandes Ignacio
    • Journal Title

      Transactions of the Japanese Society for Medical and Biological Engineering

      Volume: 49(6) Pages: 815-828

    • Related Report
      2011 Annual Research Report
  • [Presentation] The effects of IK1 blockade on the dynamics of spiral wave reentin ventricles of isolated rabbit hearts2013

    • Author(s)
      NIWA Ryoko
    • Organizer
      第90回日本生理学会大会
    • Place of Presentation
      東京
    • Year and Date
      2013-03-29
    • Related Report
      2012 Final Research Report
  • [Presentation] Atrial selectivity in sodium channel block by amidarone2013

    • Author(s)
      SUZUKI Tomoyuki
    • Organizer
      Biophysical Society 57th Annual Meeting
    • Place of Presentation
      Philadelphia,USA
    • Year and Date
      2013-02-03
    • Related Report
      2012 Final Research Report
  • [Presentation] Atrial selectivity in sodium channel block by amiodarone2013

    • Author(s)
      Suzuki Tomoyuki
    • Organizer
      Biophysical Society 57th Annual Meeting
    • Place of Presentation
      Philadelphia
    • Related Report
      2012 Annual Research Report
  • [Presentation] The effects of IK1 blockade on the dynamics of spiral wave reentry in ventricles of isolated rabbit hearts2013

    • Author(s)
      Niwa Ryoko
    • Organizer
      第90回日本生理学会大会
    • Place of Presentation
      東京
    • Related Report
      2012 Annual Research Report
  • [Presentation] ヒト iPS 細胞を用いた遺伝性不整脈疾患モデルの作成と病態解明2012

    • Author(s)
      黒田裕介
    • Organizer
      第37回東海不整脈研究会
    • Place of Presentation
      名古屋
    • Year and Date
      2012-09-15
    • Related Report
      2012 Final Research Report
  • [Presentation] IK1 遮断が心室筋の活動電位とスパイラル・リエントリーに及ぼす作用2012

    • Author(s)
      丹羽良子
    • Organizer
      第139回日本循環器学会東海地方会
    • Place of Presentation
      浜松
    • Year and Date
      2012-07-07
    • Related Report
      2012 Final Research Report
  • [Presentation] Disease characterization using long QT syndrome-specific induced pluripotent stem cells2011

    • Author(s)
      EGASHIRA Toru
    • Organizer
      American Heart Association Scientific Sessions 2011
    • Place of Presentation
      Orlando, USA
    • Year and Date
      2011-11-12
    • Related Report
      2012 Final Research Report
  • [Presentation] Atrial selectivity in sodium channel block by amiodarone2011

    • Author(s)
      SUZUKI Tomoyuki
    • Organizer
      ESC Congress 2011
    • Place of Presentation
      Paris, France
    • Year and Date
      2011-08-27
    • Related Report
      2012 Final Research Report
  • [Presentation] Atrial selectivity in sodium channel block by amiodarone2011

    • Author(s)
      SUZUKI Tomoyuki
    • Organizer
      the Japanese Circulation Society
    • Place of Presentation
      横浜
    • Year and Date
      2011-08-03
    • Related Report
      2012 Final Research Report
  • [Presentation] Molecular analysis of long QT syndromes type 1 patient specific induced pluripotent stem cell-derived cardiomyocyte2011

    • Author(s)
      KAMIYA Kaichiro
    • Organizer
      The 75th Annual Scientific Meeting of the Japanese Circulation Society Special Session
    • Place of Presentation
      横浜
    • Year and Date
      2011-08-03
    • Related Report
      2012 Final Research Report
  • [Presentation] アミオダロン類似新規化合物の薬効2011

    • Author(s)
      丹羽良子, 他
    • Organizer
      第6回東海アミオダロン研究会
    • Place of Presentation
      名古屋
    • Year and Date
      2011-02-04
    • Related Report
      2010 Annual Research Report
  • [Presentation] Molecular analysis of long QT syndromes type 1 patient specific induced pluripotent stem cell-derived cardiomyocyte.2011

    • Author(s)
      Kamiya Kaichiro
    • Organizer
      The 75th Annual Scientific Meeting of the Japanese Circulation Society Special Session
    • Place of Presentation
      横浜
    • Related Report
      2011 Annual Research Report
    • Invited
  • [Presentation] Atrial selectivity in sodium channel block by amiodarone.2011

    • Author(s)
      Suzuki Tomoyuki
    • Organizer
      The 75th Annual Scientific Meeting of the Japanese Circulation Society
    • Place of Presentation
      横浜
    • Related Report
      2011 Annual Research Report
  • [Presentation] Atrial selectivity in sodium channel block by amiodarone.2011

    • Author(s)
      Suzuki Tomoyuki
    • Organizer
      ESC Congress 2011
    • Place of Presentation
      Paris
    • Related Report
      2011 Annual Research Report
  • [Presentation] Disease characterization using long QT syndrome-specific induced pluripotent stem cells.2011

    • Author(s)
      Egashira Toru
    • Organizer
      American Heart Association Scientific Sessions 2011
    • Place of Presentation
      Orlando
    • Related Report
      2011 Annual Research Report
  • [Presentation] Amiodaroneによる心房選択的ナトリウム電流抑制効果2010

    • Author(s)
      鈴木智之, 他
    • Organizer
      第27回日本心電学会学術集会
    • Place of Presentation
      大分
    • Year and Date
      2010-10-08
    • Related Report
      2010 Annual Research Report
  • [Presentation] アミオダロンによる心房選択的ナトリウム電流抑制効果2010

    • Author(s)
      鈴木智之, 他
    • Organizer
      第135回日本循環器学会東海地方会
    • Place of Presentation
      名古屋
    • Year and Date
      2010-07-03
    • Related Report
      2010 Annual Research Report
  • [Presentation] IK1遮断が心室筋の活動電位とスパイラル・リエントリーに及ぼす作用

    • Author(s)
      丹羽良子
    • Organizer
      第139回日本循環器学会東海地方会
    • Place of Presentation
      浜松
    • Related Report
      2012 Annual Research Report
  • [Presentation] ヒトiPS細胞を用いた遺伝性不整脈疾患モデルの作成と病態解明

    • Author(s)
      黒田裕介
    • Organizer
      第37回東海不整脈研究会
    • Place of Presentation
      名古屋
    • Related Report
      2012 Annual Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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