The investigation of altered Ca2+ handling by the selective modulation of Ca2+ uptake rate of sarcoplasmic reticulum

• Project/Area Number: 23790255
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General physiology
• Research Institution: Jikei University School of Medicine
• Principal Investigator: MORIMOTO Satoshi 東京慈恵会医科大学, 医学部, 助教 (30594593)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 細胞内Ca2+動態 / 心筋筋小胞体 / ATP依存性筋小胞体Ca2+ポンプ / 国際情報交換 / 国際情報交流

Research Abstract

We investigated the role of the alteration of sarcoplasmic reticulum (SR) which is known to be a cause of cardiac dysfunction in failing heart. We used saponin-treated thin trabeculae obtained from mice hearts with overexpression of SR-Ca2+ ATPase (SERCA-TG) and sarcolipin (SLN-TG), respectively. Ca2+ uptake rate was faster in SERCA-TG and slower in SLN-TG. Maximal Ca2+ content, Ca2+ induced Ca2+ release and Ca2+ leak were not altered in SERCA-TG and SLN-TG. In the papillary muscle experiment using Ca2+ sensitive photoprotein aequorin, peak tension and peak amplitude of Ca2+ transient were increased in SERCA-TG and decreased in SLN-TG. Relaxation time of tension and decline of Ca2+ transient were accelerated in SERCA-TG and prolonged in SLN-TG. Thus, we concluded that selective modulation of Ca2+ uptake into SR influenced the amplitude and time course of Ca2+ transient and tension, however, it did not influence maximal Ca2+ content, Ca2+ induced Ca2+ release and Ca2+ leak of SR.

Research Products

• [Journal Article] Genetic modulation of the SERCA activity does not affect the Ca2+ leak from the cardiac sarcoplasmic reticulum. (2014)
  • Author(s): Morimoto S, Hongo K, Kusakari Y, Komukai K, Kawai M, O-Uchi J, Nakayama H, Asahi M, Otsu K, Yoshimura M, Kurihara S.
  • Journal Title: Cell Calcium. Volume: 55 Issue: 1 Pages: 17-23
  • DOI: 10.1016/j.ceca.2013.10.005
  • Peer Reviewed / Open Access
• [Presentation] Selective modulation of SERCA did not affect the Ca2+ leak from the sarcoplasmic reticulum in transgenic mouse models (2014)
  • Author(s): Morimoto S, Hongo K, Kusakari Y, Komukai K, Kawai M, Kurihara S, Yoshimura M
  • Organizer: American Heart Association Scientific Sessions 2012 (米国心臓学会2012)
  • Place of Presentation: Los Angeles, CA, USA
  • Year and Date: 2014-11-04
• [Presentation] SERCAもしくはsarcolipinの過剰発現はマウス心筋におけるCa2+誘発性Ca2+放出とCa2+リークに影響を与えない (2014)
  • Author(s): 森本智,本郷賢一,草刈洋一郎,小武海公明,川井真,吉村道博,栗原敏
  • Organizer: 第91回日本生理学会大会
  • Place of Presentation: 鹿児島県鹿児島市
  • Year and Date: 2014-03-16
• [Presentation] Modulation of Ca2+ uptake by changing of SERCA activity in mouse myocardium did not alter Ca2+ leak from sarcoplasmic reticulum in physiological condition (2013)
  • Author(s): Morimoto S, Kusakari Y, O-Uchi J, Komukai K, Kawai M, Yoshimura M, Hongo K, Kurihara S
  • Organizer: IUPS2013 (第37回国際生理学会議)
  • Place of Presentation: Birmingham, UK
  • Year and Date: 2013-07-22
• [Presentation] Selective modulation of SERCA did not affect the Ca2+ leak from the sarcoplasmic reticulum in transgenic mouse models
  • Author(s): Morimoto S, Hongo K, Kusakari Y, Komukai K, Kawai M, Kurihara S, Yoshimura M.
  • Organizer: American Heart Association
  • Place of Presentation: Los Angeles, CA, USA.