Parity check by gap junctions maintains normal cardiac conduction in sinoatrial node

• Project/Area Number: 23591091
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Tokyo Women's Medical University
• Principal Investigator: NISHII Akiko 東京女子医科大学, 医学部, 助教 (80408608)
• Co-Investigator(Renkei-kenkyūsha): NISHII Kiyomasa 防衛医科大学校, 医学部, 助教 (20264020)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: ギャップジャンクション / コネキシン45 / 洞結節 / パリティ保証機構 / ノックアウトマウス / 伝導障害 / コネキシン / 刺激伝導系 / パリティ保障機構

Research Abstract

Gap junctions (GJ) are intercellular pathway consisted of protein called connexins (Cx). Cx45 is distributed in whole heart in early embryonic stage and it is restricted in cardiac conduction system in the adult heart. We proposed that parity check by Cx45 is important to maintain normal cardiac conduction. To verify this hypothesis, we built region and time specific Cx45 knockout mice. Both in embryonic and adult heart, Cx45 knockout showed abnormal cardiac conduction. The data are in agreement with the hypothesis.

Research Products

• [Journal Article] A connexin40 mutation associated with a malignant variant of progressive familial heart block type I. (2012)
  • Author(s): Delmar M, Makita N
  • Journal Title: Circ Arrhythm Electrophysiol. Volume: (in press) Pages: 163-172
  • DOI: 10.1161/circep.111.967604
  • NAID: 120004397540
  • Peer Reviewed
• [Journal Article] A crucial role of activin A-mediated growth hormone suppression in mouse and human heart failure (2011)
  • Author(s): Fukushima N, Matsuura K, Akazawa H, Honda A, Nagai T, Takahashi T, Seki A, Murasaki KM, Shimizu T, Okano T, Hagiwara N, Komuro I
  • Journal Title: PLoS ONE Volume: 6
  • DOI: 10.1371/journal.pone.0027901
  • Peer Reviewed
• [Presentation] 網膜電気シナプスはカルシウム依存転写因子NFATの活性化に必要である (2014)
  • Author(s): 西井清雅、関明子、David L. Paul、萩原誠久、小林靖
  • Organizer: 第119回日本解剖学会総会・全国学術集会
  • Place of Presentation: 自治医科大学(下野)(3/27-29)
  • Year and Date: 2014-03-29
• [Presentation] Cx knock-outと不整脈. Role of connexins on cardiac arrhythmia(シンポジウム:心筋ギャップ結合機能調節機構とその病態,招待) (2014)
  • Author(s): 関明子、西井清雅、柴田洋三郎、小林靖、萩原誠久
  • Organizer: 第91回日本生理学会大会
  • Place of Presentation: 鹿児島大学(鹿児島)(3/16-18)
  • Year and Date: 2014-03-16
• [Presentation] Role of connexins on cardiac arrhythmia (2014)
  • Author(s): 関 明子、西井 清雅、柴田 洋三郎、小林 靖、萩原 誠久
  • Organizer: 第91回日本生理学会大会
  • Place of Presentation: 鹿児島大学（鹿児島）
  • Invited
• [Presentation] 網膜電気シナプスはカルシウム依存転写因子NFATの活性化に必要である (2014)
  • Author(s): 西井 清雅、関 明子、David L. Paul、萩原 誠久、小林 靖
  • Organizer: 第119回日本解剖学会総会・全国学術集会
  • Place of Presentation: 自治医科大学（下野）
• [Presentation] Connexin45 conducts essential myocardial functions during heart development (2013)
  • Author(s): 西井清雅、関明子、熊井まどか、森本幸生、三輪岳志、萩原誠久、柴田洋三郎、小林靖
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 大阪大学(神戸)(12/3-6)
  • Year and Date: 2013-12-03
• [Presentation] Connexin45 conducts essential myocardial functions during heart development. (2013)
  • Author(s): 西井 清雅、関 明子、熊井 まどか、森本 幸生、三輪 岳志、萩原 誠久、柴田 洋三郎、小林 靖
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 大阪大学（神戸）
• [Presentation] Inhibition of Activin A is the Novel Therapeutic Target for Heart Failure. (2011)
  • Author(s): Fukushima N、Matsuura K、Akazawa H、Honda A、Nagai T、Takahashi M、 Seki A、Murasaki K、Shimizu T、Okano M、Hagiwara N、 Komuro I.
  • Organizer: Scientific sessions 2011. American Heart Association
  • Place of Presentation: Orland, Florida, USA