Development of mathematical model of a Human atrial myocyte to evaluate new antiarrhythmic drugs for atrial fibrillation

• Project/Area Number: 20790206
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: General pharmacology
• Research Institution: Osaka University
• Principal Investigator: MURAKAMI Shingo Osaka University, 医学系研究科, 助教 (40437314)
• Project Period (FY): 2008 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2009: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 心臓 / 不整脈 / 抗不整脈 / 心房細動 / シミュレーション / 抗不整脈薬

Research Abstract

In this study, I have developed a mathematical model of a Human atrial myocyte. Since characteristics of atrial myocyte differ among animals, the developed model allows us to evaluate effects of antiarrhythmic drug specifically for human. Although human atrial myocytes are difficult to obtain for experiments, by using the developed model, we can examine effects of virtual drug profiles in human atrial myocytes. The developed model may improve efficiency of drug development.

Research Products

• [Journal Article] Inwardly rectifying potassium channels: their structure, function and physiological roles (2010)
  • Author(s): Hiroshi Hibino, Atsushi Inanobe, Kazuharu Furutani, Shingo Murakami, Ian Findlay, Yoshihisa Kurachi
  • Journal Title: Physiological review 90 Pages: 291-366
  • Peer Reviewed
• [Journal Article] Inwardly rectifying potassium channels : their structure, function, and physiological roles. (2010)
  • Author(s): HibinoH, Inanobe A, Furutani K, Murakami S, Findlay I, Kurachi Y.
  • Journal Title: Physiol Rev 90 Pages: 291-366
  • Peer Reviewed
• [Journal Article] ヒト心房活動電位モデルを用いた各種IKr遮断薬とIKur遮断薬による活動電位延長作用の検討 (2009)
  • Author(s): 村上慎吾、辻前賢司、鈴木慎悟、倉智嘉久
  • Journal Title: 心電図 29 Pages: 126-132
  • Peer Reviewed
• [Journal Article] 3次元心室壁モデルにおけるスパイラルリエントリーのin silicoフィラメント動態解析～致死的不整脈防御機構としての心室較差の電気生理学的意義～ (2008)
  • Author(s): 原口亮, 芦原貴司, 藤堂貴弘, 難波経豊, 村上慎吾, 倉智嘉久, 中沢一雄
  • Journal Title: 生体医工学 46(6) Pages: 660-666
  • NAID: 110007098783
  • Peer Reviewed
• [Journal Article] In Silico Prediction of the Chemical Block of Human Ether-a-Go-Go-Related Gene (hERG) K+ Current (2008)
  • Author(s): Atsushi Inanobe, Narutoshi Kamiya, Shingo Murakami, Yoshifumi Fukunishi, Haruki Nakamura, Yoshihisa Kurachi
  • Journal Title: J Physiol Sci 58 Pages: 459-470
  • NAID: 10027710790
  • Peer Reviewed
• [Journal Article] Microstructure-based monte carlo simulation of Ca2+ dynamis evoking cardiac culcium channel inactivation (2008)
  • Author(s): Toshihiro Kawazu, Shingo Murakami, Satomi Adachi-Akahane, Ian Findlay, Rachid Ait-Haddou, Yoshihisa Kurachi, Taishin Nomura
  • Journal Title: J Physiol Sci 58 Pages: 471-480
  • Peer Reviewed
• [Journal Article] Physiological modulation of voltage-dependent inactivation in the cardiac muscle L-type calcium channel: a modelling study (2008)
  • Author(s): Ian Findlay, Shingo Suzuki, Shingo Murakami, Yoshihisa Kurachi
  • Journal Title: Progress in Biophysics & Molecular Biology 96 Pages: 482-498
  • Peer Reviewed
• [Journal Article] In silico study on the effects of IKur block kinetics on prolongation of human action potential after atrial fibrillation-induced electrical-remodeling (2008)
  • Author(s): Kenji Tsujimae, Shingo Murakami, Yoshihisa Kurachi
  • Journal Title: AJP - Heart and Circulatory Physiology 294(2)
  • Peer Reviewed
• [Journal Article] In silico study on the effects of IKur block kinetics on prolongation ofhuman action potential after atrial fibrillation-induced electrical-remodeling (2008)
  • Author(s): Tsujimae K. Murakami S. Kurachi Y.
  • Journal Title: Am J Physiol Heart Circ Physiol 294
  • Peer Reviewed
• [Journal Article] Physiological modulation of voltage-dependent inactivation in the cardiac muscle L-type calcium channel : a modelling study (2008)
  • Author(s): Findlay I, Suzuki S, MurakamiS, Kurachi Y.
  • Journal Title: Prog Biophys Mol Bio 96 Pages: 482-498
  • Peer Reviewed
• [Journal Article] In silico assessment for drug-induction of cardiac arrhythmia (2008)
  • Author(s): Suzuki S, Murakami S, Tsujimae K, Findlay I, Kurachi Y.
  • Journal Title: Prog Biophys Mol Bio 98 Pages: 52-60
  • Peer Reviewed
• [Journal Article] Microstructure-based monte carlo simulation of Ca^<2+> dynamis evoking cardiac culcium channel inactivation (2008)
  • Author(s): Kawazu T, Murakami S, Adachi-Akahane S, Findlay I, Ait-Haddou R, Kurachi Y, Nomura T.
  • Journal Title: J Physiol Sci 58 Pages: 571-580
  • Peer Reviewed
• [Journal Article] Cellular modeling : experiments and simulation to develop the physiological model for G-protein control of Cardiac muscarinic K+ channels in mammalian atrial cells.
  • Author(s): Murakami S, Suzuki S, Ishii M, Inanobe A, Kurachi Y.
  • Journal Title: Philos Transact A (印刷中)
  • Peer Reviewed
• [Journal Article] 薬物誘発性不整脈の発生危険度予測システムの開発
  • Author(s): 村上慎吾, 鈴木慎悟, 上島豊, 野村泰伸, 倉智嘉久
  • Journal Title: 生体医工学 (印刷中)
  • NAID: 10031199751
  • Peer Reviewed
• [Presentation] ArrhythmoPredictor: A web-based simulation database system for prediction of drug induced arrhythmia (2009)
  • Author(s): Shingo Murakami, Shingo Suzuki, Kunichika Tsumoto, Yoshihisa Kurachi
  • Organizer: 第26回国際心臓研究学会(ISHR)日本部会
  • Year and Date: 2009-12-04
• [Presentation] ArrhythmoPredictor : A web-based simulation database system for prediction of drug induced arrhythmia (2009)
  • Author(s): Shingo Murakami, Shingo Suzuki, Kunichika Tsumoto, Yoshihisa Kurachi
  • Organizer: 第26回国際心臓研究学会(ISHR)日本部会
  • Place of Presentation: Sapporo
  • Year and Date: 2009-12-04
• [Presentation] 2変数表示法による薬物誘発不整脈発生危険度の予測システムの開発 (2009)
  • Author(s): 村上慎吾, 鈴木慎悟, 津元国親, 上島豊. 野村泰伸, 倉智嘉久
  • Organizer: 生体医工学シンポジウム2009
  • Year and Date: 2009-09-18
• [Presentation] 2変数表示法による薬物誘発不整脈発生危険度の予測システムの開発 (2009)
  • Author(s): 村上慎吾, 鈴木慎悟, 津元国親, 上島豊, 野村泰伸, 倉智嘉久
  • Organizer: 生体医工学シンポジウム2009
  • Place of Presentation: 千葉
  • Year and Date: 2009-09-18
• [Presentation] Cardiac excitation and neural control (2009)
  • Author(s): Murakami S. Suzuki S. Findlay I. Kurachi Y.
  • Organizer: The 36th Congress of the International Union of Physiological Sciences
  • Year and Date: 2009-07-28
• [Presentation] Cardiac excitation and neural control (2009)
  • Author(s): Murakami S., Suzuki S., Findlav I., Kurachi Y
  • Organizer: The 36th Congress of the International Union of Physiological Sciences.
  • Place of Presentation: Kyoto
  • Year and Date: 2009-07-28
• [Presentation] 薬物誘発不整脈発生危険度の予測システムArrhythmoPredictor (2009)
  • Author(s): 村上慎吾, 鈴木慎悟, 津元国親, 上島豊. 野村泰伸, 倉智嘉久
  • Organizer: 第26回日本心電学会学術集会
  • Year and Date: 2009-07-02
• [Presentation] 薬物誘発不整脈発生危険度の予測システムArrhythmoPredictor (2009)
  • Author(s): 村上慎吾, 鈴木慎悟, 津元国親, 上島豊.野村泰伸, 倉智嘉久
  • Organizer: 第26回日本心電学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2009-07-02
• [Presentation] 薬物誘発不整脈発生危険度の予測システムArrhythmoPredictorの開発 (2009)
  • Author(s): 村上慎吾、鈴木慎悟、津元国親、上島豊、野村泰伸、倉智嘉久
  • Organizer: 第48回日本生体医工学会大会
  • Year and Date: 2009-04-25
• [Presentation] 薬物誘発不整脈発生危険度の予測システムArrhythmoPredictorの開発 (2009)
  • Author(s): 村上慎吾, 鈴木慎悟, 津元国親, 上島豊.野村泰伸, 倉智嘉久
  • Organizer: 第48回日本生体医工学会大会
  • Place of Presentation: 東京
  • Year and Date: 2009-04-25
• [Presentation] ヒト心房細胞モデルによるIKur阻害剤の活動電位延長作用の検討 (2009)
  • Author(s): 村上慎吾、辻前賢司、倉智嘉久
  • Organizer: The effects of IKur block kinetics on prolongation of human action potential duration. 第82回日本薬理学会年会
  • Year and Date: 2009-03-16
• [Presentation] ヒト心房活動電位モデルを用いた各種IKr阻害剤とIKur阻害剤による活動電位延長作用の検討 (2008)
  • Author(s): 村上慎吾
  • Organizer: 第25回日本心電学会学術集会
  • Year and Date: 2008-11-02
• [Presentation] ヒト心房活動電位モデルを用いた各種恥阻害剤とIKur阻害剤による活動電位延長作用の検討 (2008)
  • Author(s): 村上慎吾、辻前賢司、鈴木慎悟、倉智嘉久
  • Organizer: 第25回日本心電学会学術集会
  • Place of Presentation: 新潟
  • Year and Date: 2008-11-02
• [Presentation] ヒト心房活動電位数学モデルを用いた、各種IKr阻害剤による活動電位延長作用の刺激頻度依存性の検討 (2008)
  • Author(s): 辻前賢司、鈴木慎悟、村上慎吾、倉智嘉久
  • Organizer: 第113回日本薬理学会近畿部会
  • Year and Date: 2008-06-20
• [Book] 臨床医工学スキルアップ講座
  • Author(s): 村上慎吾、津元国親、倉智嘉久
  • Publisher: 大阪大学出版(印刷中)