Exploration of anti-arrhythmic drugs acting on RyR2 using myocardium and cultured cells.

• Project/Area Number: 24590331
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General pharmacology
• Research Institution: Juntendo University
• Principal Investigator: KUREBAYASHI Nagomi 順天堂大学, 医学部, 准教授 (50133335)
• Co-Investigator(Renkei-kenkyūsha): MURAYAMA Takashi 順天堂大学, 医学部, 准教授 (10230012) ; MORIMOTO Sachio 九州大学, 医学部, 准教授 (50202362) ; NAKAZATO Yuji 順天堂大学, 医学部, 教授 (30266035)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: リアノジン受容体 / 不整脈 / カルシウム / カテコラミン誘発性多型性心室頻拍 / 抗不整脈薬 / 心臓 / 心筋 / 筋小胞体 / ライブイメージング / Ca2+遊離

Outline of Final Research Achievements

The agents acting on type 2 ryanodine receptor (RyR2) are expected to be good anti-arrhythmic and/or preventive drugs. In this study, we developed experimental systems that are useful for search of anti-arrhythmic drugs acting on RyR2; one is arrhythmogenic myocardium and the other is a cultured cell system expressing recombinant RyR2 molecules.

Research Products

• [Journal Article] Effects of candesartan on electrical remodeling in the hearts of inherited dilated cardiomyopathy model mice. (2014)
  • Author(s): Odagiri, F., H. Inoue, M. Sugihara, T. Suzuki, T. Murayama, T. Shioya, M. Konishi, Y. Nakazato, H. Daida, T. Sakurai, S. Morimoto, N. Kurebayashi
  • Journal Title: PLoS One Volume: 9 Issue: 7 Pages: e101838-e101838
  • DOI: 10.1371/journal.pone.0101838
  • Peer Reviewed / Open Access
• [Journal Article] Assembly of the cochlear gap junction macromolecular complex requires connexin 26. (2014)
  • Author(s): Kamiya K, Yum SW, Kurebayashi N, Muraki M, Ogawa K, Karasawa K, Miwa A, Guo X, Gotoh S, Sugitani Y, Yamanaka H, Ito-Kawashima S, Iizuka T, Sakurai T, Noda T, Minowa O, Ikeda K.
  • Journal Title: J Clin Invest, Volume: 124 Issue: 4 Pages: 1598-1607
  • DOI: 10.1172/jci67621
  • Peer Reviewed / Open Access
• [Journal Article] キーワード解説：カルシウム・膜電位イメージング. (2014)
  • Author(s): 呉林なごみ
  • Journal Title: 日本薬理学雑誌 Volume: 143 Pages: 45-46
  • Open Access
• [Journal Article] Usefulness of running wheel for detection of congestive heart failure in dilated cardiomyopathy mouse model (2014)
  • Author(s): Sugihara M, Odagiri F, Suzuki T, Murayama T, Nakazato Y, Unuma K, Yoshida K, Daida H, Sakurai T, Morimoto S, Kurebayashi N.
  • Journal Title: PLoS One Volume: 8(1) Issue: 1 Pages: e55514-e55514
  • DOI: 10.1371/journal.pone.0055514
  • Peer Reviewed
• [Journal Article] キーワード解説：カルシウム・膜電位イメージング (2014)
  • Author(s): 呉林なごみ
  • Journal Title: 日本薬理学雑誌 Volume: 143 Pages: 45-46
  • Peer Reviewed
• [Journal Article] Inositol 1,4,5-Trisphosphate receptor regulates replication, differentiation, infectivity, and virulence of the parasitic protist Trypanosoma cruzi (2013)
  • Author(s): Hashimoto M
  • Journal Title: Mol Microbiology Volume: 87(6) Issue: 6 Pages: 1133-50
  • DOI: 10.1111/mmi.12155
  • Peer Reviewed
• [Journal Article] Multistep ion channel remodeling and lethal arrhythmia precede heart failure in a mouse model of inherited dilated cardiomyopathy (2012)
  • Author(s): Suzuki T, Shioya T, Murayama T, Sugihara M, Odagiri F, Nakazato Y, Nishizawa H, Chugun A, Sakurai T, Daida H, Morimoto S, Kurebayashi N
  • Journal Title: PLoS ONE Volume: 7 Issue: 4 Pages: e35353-e35353
  • DOI: 10.1371/journal.pone.0035353
  • Peer Reviewed
• [Journal Article] 筋小胞体のCa2+放出機構の最近の進歩 (2012)
  • Author(s): 呉林なごみ, 村山尚
  • Journal Title: 生体の科学 Volume: 63 Pages: 374-375
• [Presentation] ２型リアノジン受容体の不整脈原性変異はCICR活性とCa2+ 動態にどのような影響を及ぼすか？ (2015)
  • Author(s): 呉林なごみ, 村山尚, 太田亮作, 山下富義, 鈴木純二, 金丸和典, 飯野正光, 櫻井隆
  • Organizer: 第88回 日本薬理学会年会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-03-19
• [Presentation] Effects of arrhythmogenic mutations on Ca2+-induced Ca2+ release activities of type 2 ryanodine receptors. (2015)
  • Author(s): Kurebayashi, N., T. Murayama, J. Suzuki, K. Kanemaru, M. Iino, T. Sakurai
  • Organizer: Biophysical society, 59th Annual Meeting
  • Place of Presentation: ボルチモア、アメリカ合衆国
  • Year and Date: 2015-02-11
• [Presentation] Effects of MH and CCD mutations in the central region on RyR1 channels. (2015)
  • Author(s): Takashi Murayama, Nagomi Kurebayashi, Toshiko Yamazawa, Hideto Oyamada, Junji Suzuki, Kazunori Kanemaru, Katsuji Oguchi, Masamitsu Iino, and Takashi Sakurai
  • Organizer: Biophysical Society 59th Annual Meeting
  • Place of Presentation: ボルチモア、アメリカ合衆国
  • Year and Date: 2015-02-09
• [Presentation] 心筋型リアノジン受容体（RyR2）不整脈原性変異のCa2+ 動態とCICR活性に対する効果 (2014)
  • Author(s): 呉林なごみ, 村山尚, 太田亮作, 山下富義, 鈴木純二, 金丸和典, 飯野正光, 櫻井隆
  • Organizer: 第24回 日本循環薬理学会
  • Place of Presentation: 山形テルサ、山形市
  • Year and Date: 2014-12-05
• [Presentation] 心室性不整脈を誘発する2型リアノジン受容体変異体のCa2+遊離の特性 (2014)
  • Author(s): 呉林なごみ 村山尚 鈴木純二 金丸和典 飯野正光 櫻井隆
  • Organizer: 第91回日本生理学会大会
  • Place of Presentation: 鹿児島
• [Presentation] 不整脈原性2型リアノジン受容体のCICR特性 (2014)
  • Author(s): 呉林なごみ 村山尚 鈴木純二 金丸和典 飯野正光 櫻井隆
  • Organizer: 第87回日本薬理学会年会
  • Place of Presentation: 仙台
• [Presentation] Divergent effects of disease associated mutations on type 2 ryanodine receptor channel. (2014)
  • Author(s): Kurebayashi, N Murayama, T Uehara, A Yasukochi, M Sakura,i T
  • Organizer: 58th Biophysical Society Annual Meeting
  • Place of Presentation: サンフランシスコ、米国
• [Presentation] Effects of candesartan on progression of electrical remodeling in the hearts of inherited DCM model mice (2014)
  • Author(s): Nagomi Kurebayashi, Fiminori Odagiri, Hana Inoue, Masami Sugihara, Takeshi Suzuki, Takashi Murayama, Takao Shioya, Masato Konishi, Yuji Nakazato, Hiroyuki Daida, Takashi Sakurai, Sachio Morimoto,
  • Organizer: 17th World Congress of Pharmacology
  • Place of Presentation: ケープタウン、南アフリカ共和国
• [Presentation] 拡張型心筋症モデルマウス心臓の電気的リモデリングに対するカンデサルタンの効果 (2013)
  • Author(s): 呉林なごみ, 小田切史徳, 杉原匡美, 鈴木剛, 井上華, 村山尚, 塩谷孝雄, 小西真人, 中里祐二, 代田浩之, 櫻井隆, 森本幸生
  • Organizer: 第86回日本薬理学会年会
  • Place of Presentation: 福岡
• [Presentation] 遺伝性拡張型心筋症における無症候期、突然死危険期、破綻期と、これらを左右する因子 (2013)
  • Author(s): 呉林なごみ
  • Organizer: 第90回日本生理学会大会
  • Place of Presentation: 東京 船堀
• [Presentation] FFECTS OF ANGIOTENSIN II RECEPTOR BLOCKER ON THE PROGRESSION OF ELECTRICAL REMODELING IN HEARTS OF INHERITED DCM MODEL MICE. (2013)
  • Author(s): Odagiri F, Inoue H, Sugihara M, Suzuki T, Murayama T, Shioya T, Konishi M, Nakazato Y, Daida H, Sakurai T, Morimoto S, Kurebayashi N
  • Organizer: 57th Biophysical Society Annual Meeting Philadelphia
  • Place of Presentation: フィラデルフィア
• [Book] 不整脈学 (2012)
  • Author(s): 呉林 なごみ
  • Publisher: 南江堂
• [Remarks] 順天堂大学大学院 細胞・分子薬理学 ホームページ
  • URL: http://pharmacology.sakura.ne.jp/index.html