Arrhythmogenic mechanism of gap junctional uncoupling

• Project/Area Number: 20590860
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Nagoya University
• Principal Investigator: HONJO Haruo Nagoya University, 環境医学研究所, 准教授 (70262912)
• Co-Investigator(Renkei-kenkyūsha): KAMIYA Kaichiro 名古屋大学, 環境医学研究所, 教授 (50194973) ; TSUJI Yukiomi 名古屋大学, 環境医学研究所, 助教 (60432217) ; KODAMA Itsuo 名古屋大学, 環境医学研究所, 名誉教授 (30124720)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: ギャップ接合 / 致死性不整脈 / スパイラルリエントリー / 光学マッピング / 活動電位 / 興奮伝播 / スパイラル・リエントリー / 興奮伝導 / 湾曲効果 / 電気生理学 / 不整脈 / 空間定数 / 拡散係数 / リエントリー

Research Abstract

Arrhythmogenic mechanisms of intercellular electrical uncoupling was investigated by optical mapping of purfued rabbit hearts. Pharmacological inhibition of myocardial gap junctions stabilized the dynamics of spiral-wave reentry and facilitated its perpetuation, whereas enhancement of gap junctional coupling destabilized spiral-wave reentry and promoted its early self-termination by compromising propagation of excitation waves with strong curvature near the rotation center. These results suggest that enhancement of gap junctional coupling could be a useful strategy for the treatment of life-threatening arrhythmias in diseased hearts with gap junctional remodeling.

Research Products

• [Journal Article] Bepridil facilitates early termination of spiral-wave reentry in two-dimensional cardiac muscle through an increase of intercellular electrical coupling. (2011)
  • Author(s): Takanari H, Honjo H, Kamiya K, Kodama I
  • Journal Title: J Pharmacol Sci 115 Pages: 15-26
  • NAID: 10029891366
  • Peer Reviewed
• [Journal Article] Bepridil facilitates early termination of spiral-wave reentry in two-dimensional cardiac muscle through an increase of intercellular electrical coupling. (2011)
  • Author(s): Takanari H, et al.
  • Journal Title: Journal of Pharmacological Sciences Volume: 115 Pages: 15-26
  • Peer Reviewed
• [Journal Article] Acute amiodarone promotes drift and early termination of spiral wave reentry. (2010)
  • Author(s): Nakagawa H, Honjo H, Kamiya K, Kodama I
  • Journal Title: Heart Vessels. 25 Pages: 338-347
  • Peer Reviewed
• [Journal Article] Acute amiodarone promotes drift and early termination of spiral wavereentry. (2010)
  • Author(s): Nakagawa H, et al.
  • Journal Title: Heart and Vessels Volume: 25 Pages: 338-347
  • Peer Reviewed
• [Journal Article] Early termination of spiral wave reentry by combined blockade of Na^+ and L-type Ca2^+ currents in a perfused twodimensional epicardial layer of rabbit ventricular myocardium.` (2009)
  • Author(s): Ishiguro YS, Honjo H, (8名) Kamiya K, Kodama I
  • Journal Title: Heart Rhythm 6 Pages: 684-692
  • Peer Reviewed
• [Journal Article] Early termination of spiral wave reentry by combined blockade of Na^+ and L-type Ca^<2+> currents in a perfused two-dimensional epicardial layer of rabbit ventricular myocardium (2009)
  • Author(s): Yuko S.Ishiguro, et al
  • Journal Title: Heart Rhythm 6 Pages: 684-692
  • Peer Reviewed
• [Journal Article] optical mappingによるspiral waveの解析 (2009)
  • Author(s): 本荘晴朗, 他
  • Journal Title: 心電図 29 Pages: 231-235
  • NAID: 10026293138
• [Journal Article] スパイラル・リエントリーのダイナミクスとその制御 (2009)
  • Author(s): 本荘晴朗, 他
  • Journal Title: 臨床と研究 86 Pages: 129-132
• [Journal Article] スパイラル・リエントリーと抗不整脈薬 (2009)
  • Author(s): 本荘晴朗, 他
  • Journal Title: Medical Topics Series不整脈2009 Pages: 14-24
• [Journal Article] 心房細動の電気生理学 (2008)
  • Author(s): 本荘晴朗
  • Journal Title: 臨床と研究 85 Pages: 122-124
• [Presentation] Effects of inhibition of calmodulin on intercellular electrical couplingand excitation wave propagation in ventricular myocardium (2011)
  • Author(s): Honjo H, et aL
  • Organizer: 第88回日本生理学会大会・第116回日本解剖学会総会全国学術集会
  • Place of Presentation: 要旨集
  • Year and Date: 2011-03-29
• [Presentation] Inhibition of Calmodulin increases intercellular coupling of ventricular myocardium by enhancement of connexin43 localization in intercalated disk (2010)
  • Author(s): Takanari H, et al.
  • Organizer: American Heart Association Scientific Sessions
  • Place of Presentation: Chicago, USA
  • Year and Date: 2010-11-17
• [Presentation] 心筋細胞間電気結合阻害がスパイラルリエントリーのダイナミクスに及ぼす作用:Naチャネル遮断との比較 (2010)
  • Author(s): 竹本芳雄, 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
• [Presentation] Effects of gap junctional coupling on conduction properties and spiral-wave dynamics in rabbit ventricles. (2010)
  • Author(s): Honjo H, et al.
  • Organizer: 第87回日本生理学会大会
  • Place of Presentation: 盛岡
  • Year and Date: 2010-05-21
• [Presentation] Increased electrical coupling destabilizes spiral-wave reentry in favor ofits early termination through inhibition of wave propagation near therotation center. (2010)
  • Author(s): Takemoto Y, et al.
  • Organizer: Heart Rhythm 2010
  • Place of Presentation: Denver, USA
  • Year and Date: 2010-05-15
• [Presentation] W7, a Calmodulin antagonist, destabilizes spiral-wave reentry and promotes its early termination through an increase of intercellular electrical coupling (2010)
  • Author(s): Hiroki Takanari, et al
  • Organizer: The 74th Annual Scientific Meeting of the Japanese Circulation Society
  • Place of Presentation: Kyoto
  • Year and Date: 2010-03-07
• [Presentation] Decreased intercellular coupling stabilizes 2-dimensional spiral-wave reentry, whereas increased coupling facilitates unpinning and early termination of the reentry (2010)
  • Author(s): Yoshio Takemoto, et al
  • Organizer: The 74th Annual Scientific Meeting of the Japanese Circulation Society
  • Place of Presentation: Kyoto
  • Year and Date: 2010-03-07
• [Presentation] Increased electrical coupling destabilizes spiral-wave reentry in favor of its early termination through inhibition of wave propagation near the rotation center. (2010)
  • Author(s): Takemoto Y, Honjo H, Kamiya K, Kodama I
  • Organizer: Heart Rhythm2010.
  • Place of Presentation: Denver, USA
• [Presentation] Inhibition of calmodulin increases intercellular coupling of ventricular myocardium by enhancement of connexin43 localization in intercalated disk. (2010)
  • Author(s): Takanari H, Honjo H, Kodama I, Kamiya K
  • Organizer: American Heart Association Scientific Sessions.
  • Place of Presentation: Chicago, USA
• [Presentation] 虚血心におけるスパイラル・リエントリー (2009)
  • Author(s): 本荘晴朗
  • Organizer: 第23回冠疾患学会
  • Place of Presentation: 大阪
  • Year and Date: 2009-12-18
• [Presentation] Bepridil destabilizes spiral-wave reentry and facilitates its early termination in cardiac muscle through an increase of intercellular coupling (2009)
  • Author(s): Hiroki Takanari, et al.
  • Organizer: The 13th Congress of the International Society for Holter and Noninvasive Electrocardiology
  • Place of Presentation: Orlando, USA
  • Year and Date: 2009-11-16
• [Presentation] Gap junctional uncoupling stabilizes 2-dimensional spiral-wave reentry in favor of its persistence (2009)
  • Author(s): Yoshio Takemoto, et al.
  • Organizer: The 2nd Asia Pacific Heart Rhythm Society Scientific Sessions
  • Place of Presentation: Beijing, China
  • Year and Date: 2009-10-23
• [Presentation] 細胞間電気結合が心室筋の興奮伝導とスパイラル・リエントリーに及ぼす作用 (2009)
  • Author(s): 本荘晴朗, 他
  • Organizer: 第25回心電情報処理ワークショップ
  • Place of Presentation: 神戸
  • Year and Date: 2009-10-17
• [Presentation] A unique modification of spiral wave reentry by bepridil : relating to ion channel blocking action and inhibition of calmodulin (2009)
  • Author(s): Hiroki Takanari, et al.
  • Organizer: European Society of Cardiology 2009
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 2009-09-01
• [Presentation] Dynamics of spiral wave reentry (2009)
  • Author(s): Haruo Honjo, et al.
  • Organizer: The 36th International Congress of Physiological Sciences
  • Place of Presentation: Kyoto
  • Year and Date: 2009-07-30
• [Presentation] The effects of intercellular electrical uncoupling on the dynamics of spiral reentry in ventricular myocardium of isolated rabbit hearts (2009)
  • Author(s): Yoshio Takemoto, et al.
  • Organizer: The 36th International Congress of Physiological Sciences
  • Place of Presentation: Kyoto
  • Year and Date: 2009-07-30
• [Presentation] Pharmacological modification of spiral-wave reentry in rabbit heart : optical mapping analysis (2009)
  • Author(s): Itsuo Kodama, et al.
  • Organizer: The 13th Congress of the International Society for Holter and Noninvasive Electrocardiology
  • Place of Presentation: Yokohama
  • Year and Date: 2009-06-05
• [Presentation] Bepridil destabilizes spiral wave reentry in terms of prolongation of action potential duration and augmentation of intercellular electrical coupling (2009)
  • Author(s): Hiroki Takanari, et al.
  • Organizer: The 13th Congress of the International Society for Holter and Noninvasive Electrocardiology
  • Place of Presentation: Yokohama
  • Year and Date: 2009-06-05
• [Presentation] Intercellular uncoupling stabilizes spiral-wave reentry in favor of its persistence (2009)
  • Author(s): Yoshio Takemoto, et al.
  • Organizer: The 13th Congress of the International Society for Holter and Noninvasive Electrocardiology
  • Place of Presentation: Yokohama
  • Year and Date: 2009-06-05
• [Presentation] Intercellular uncoupling stabilizes spiral-wave reentry in favor of its persistence (2009)
  • Author(s): TakemotoY, et al
  • Organizer: 第73回日本循環器学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2009-03-22
• [Presentation] Bepridil destabilizes spiral wave reentry in favor of its early termination through tremendous drift of rotation center (2009)
  • Author(s): Takanari H, et al
  • Organizer: 第73回日本循環器学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2009-03-21
• [Presentation] A unique modification of spiral wave reentry by bepridil : relating to ion channel blocking action and inhibition of calmodulin. (2009)
  • Author(s): Takanari H, Honjo H, Kamiya K, Kodama I
  • Organizer: European Society of Cardiology 2009.
  • Place of Presentation: Barcelona, SPAIN
• [Presentation] Dynamics of spiral wave reentry. (2009)
  • Author(s): Honjo H, Kamiya K, Kodama I
  • Organizer: 36thInternational Congress of Physiological Sciences.
  • Place of Presentation: Kyoto(invited)
• [Presentation] The effects of intercellular electrical uncoupling on the dynamics of spiral reentry in ventricular myocardium of isolated rabbit hearts. (2009)
  • Author(s): Takemoto Y, Honjo H, Kamiya K, Kodama I
  • Organizer: 36th International Congress of Physiological Sciences.
  • Place of Presentation: Kyoto
• [Presentation] Bepridil destabilizes spiral-wave reentry in favor of its early termination through tremendous drift of rotation center. (2009)
  • Author(s): Takanari H (4名) Honjo H (1名) Kamiya K, Kodama I
  • Organizer: The 73rd Annual Scientific Meeting of the Japanese Circulation Society.
  • Place of Presentation: Osaka
• [Presentation] Intercellular uncoupling stabilizes spiral-wave reentry in favor of its persistence. (2009)
  • Author(s): Takemoto Y, Tsuji Y, Honjo H,Kamiya K, Kodama I
  • Organizer: The 73rd Annual Scientific Meeting of the Japanese Circulation Society.
  • Place of Presentation: Osaka
• [Presentation] Dynamics of spiral wave reentry (2008)
  • Author(s): Honjo H, et al
  • Organizer: International Symposium on Arrhythmias
  • Place of Presentation: 名古屋
  • Year and Date: 2008-11-29
• [Presentation] 心筋ギャップ接合阻害がスパイラル・リェントリーのダイナミクスに及ぼす作用 (2008)
  • Author(s): 竹本芳雄, 他
  • Organizer: 日本循環器学会第132回東海・第117回北陸合同地方会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-11-16
• [Presentation] Optical mappingによるspiral waveの解析 (2008)
  • Author(s): 本荘晴朗
  • Organizer: 第25回日本心電学会学術集会
  • Place of Presentation: 新潟
  • Year and Date: 2008-11-01
• [Presentation] スパイラル・リエントリーのダイナミクスと制御 (2008)
  • Author(s): 本荘晴朗
  • Organizer: 第9回九州重症不整脈研究会
  • Place of Presentation: 福岡
  • Year and Date: 2008-07-26
• [Presentation] 低カリウム下の心室スパイラル・リエントリーに対するベプリジルの作用 (2008)
  • Author(s): 高成広起, 他
  • Organizer: 第23回日本不整脈学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2008-06-01
• [Book] スパイラル・リエントリーと抗不整脈薬(Medical Topics Series 不整脈2009)(杉本恒明(監), 井上博(編)) (2009)
  • Author(s): 本荘晴朗, 児玉逸雄
  • Publisher: 大阪・東京:メディカルレビュー社