Establishment of neural factor for regulating exercise activity and cardiac hypertrophy

• Project/Area Number: 24700754
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Applied health science
• Research Institution: Oita University
• Principal Investigator: MORISHIMA Masaki 大分大学, 医学部, 助教 (40437934)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 脳内モノアミン / 心肥大 / 運動習慣 / 自発運動 / 高運動性 / DNAマイクロアレイ / 心筋肥大 / 心臓自律神経活動 / 心拍変動解析

Outline of Final Research Achievements

We established a new animal model called SPORTS rats. The aim of this study was to investigate the role of the L-type Ca2+ channel in cardiomyocytes and its relation with intracellular Ca2+-dependent signalings in cardiac adaptation responding to high physical activity. Injection of Ca2+ channel antagonist verapamil markedly decreased wheel-running activity with a reduction of heart rate in SPORTS rats. In isolated neonatal rat cardiomyocytes from SPORTS rats, spontaneous beating rate, L-type Ca2+ current, and the expression ofits mRNAs were significantly higher than those in control rat. Phosphorylation of CREB and Akt were significantly elevated in SPORTS rat myocytes in the basal condition. These results suggest that phosphorylation of the CREB via activation of PI3K/Akt signaling pathway in SPORTS rats positively regulates the L-type Ca2+ channel expression, which is responsible for the enhancement of physiological hypertrophy and chronotropy in the heart.

Research Products

• [Journal Article] Hypomagnesemic down-regulation of L-type Ca2+ channel in cardiomyocyte as an arrhythmogenic substrate in rats. (2015)
  • Author(s): Shimaoka T, Wang Y, Morishima M, Miyamoto S, Ono K
  • Journal Title: Pathophysiology Volume: 未定
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Establishment of model of Spontaneously- Running- Tokushima-Shikoku rats with left atrial thrombosis (2014)
  • Author(s): Ohnishi T, Hisaoka F, Morishima M, Takahashi A, Harada N, Mawatari K, Arai H, Yoshioka E, Toda S, Izumi K, Nakaya Y.
  • Journal Title: Journal of Toxicologic Pathology Volume: in press
  • NAID: 130003382469
  • Peer Reviewed
• [Journal Article] Enhancement of endothelial function inhibits left atrial thrombi development in an animal model of spontaneous left atrial thrombosis (2014)
  • Author(s): Mawatari K, Yoshioka E, Toda S, Yasui S, Furukawa H, Shimohata T, Ohnishi T, Morishima M, Harada N, Takahashi A, Sakaue H, Nakaya Y
  • Journal Title: Circulation journal Volume: in press
  • NAID: 130004427936
  • Peer Reviewed
• [Presentation] Role of apelin in human atrial tissue with persistent atrial fibrillation (2015)
  • Author(s): Haruyama T, Morishima M, Takanari H, Ono K
  • Organizer: 第92回日本生理学会大会
  • Place of Presentation: 神戸国際会議場(神戸市ポートアイランド)
  • Year and Date: 2015-03-21 – 2015-03-23
• [Presentation] Influence of high-cholesterol on arrhythmogenicity in mouse atrium (2015)
  • Author(s): Takahashi M, Takanari H, Morishima M, Ono K
  • Organizer: 第92回日本生理学会大会
  • Place of Presentation: 神戸国際会議場(神戸市ポートアイランド）
  • Year and Date: 2015-03-21 – 2015-03-23
• [Presentation] 心房細動におけるイオンチャネルリモデリングを制御するmicroRNA (2014)
  • Author(s): 森島真幸，岩田英理子，中田知里，塚本善之，髙成広起，宮本伸二，守山正胤，小野克重
  • Organizer: 第65回西日本生理学会
  • Place of Presentation: 琉球大学（沖縄）
  • Year and Date: 2014-10-24
• [Presentation] MicroRNA-dependent regulation of K+ channel remodeling in human cardiomyocytes with persistent atrial fibrillation. (2014)
  • Author(s): Morishima M, Iwata E, Nakada C, Tsukamoto Y, Takanari H, Miyamoto S, Moriyama M, Ono K.
  • Organizer: 第29回日本不整脈学会／第31回日本心電学会合同学術大会
  • Place of Presentation: 東京プリンスホテル(東京都港区）
  • Year and Date: 2014-07-22 – 2014-07-25
• [Presentation] 低酸素環境における心筋Ｔ型カルシウムチャネルの役割 (2014)
  • Author(s): 森島真幸、長川賢、稲垣薫克、土持裕胤、白井幹康、小野克重
  • Organizer: 第91回日本生理学会大会
  • Place of Presentation: 鹿児島大学 郡元キャンパス
• [Presentation] テストステロンは心筋においてKvLQT1チャネルの発現を増加させQT間隔を短縮させる (2014)
  • Author(s): 増田季美子、王岩、馬芳芳、森島真幸、高成広起、小野克重
  • Organizer: 第91回日本生理学会大会
  • Place of Presentation: 鹿児島大学 郡元キャンパス
• [Presentation] 脳由来神経栄養因子BDNFとその受容体TrkBの低酸素環境下心筋における発現動態 (2013)
  • Author(s): 森島真幸、藤田崇史、小野克重
  • Organizer: 第23回日本病態生理学会
  • Place of Presentation: 東京慈恵会医科大学
• [Presentation] 脳由来神経栄養因子BDNFの心臓における発現と低酸素病態下での機能 (2012)
  • Author(s): 藤田崇史、森島真幸、小野克重
  • Organizer: 第63回西日本生理学会
  • Place of Presentation: 大分市全労済ソレイユ
• [Presentation] 脳由来神経栄養因子BDNFの心臓における発現と低酸素病態下における役割
  • Author(s): 森島真幸、藤田崇史、小野克重
  • Organizer: 第12回九州脳と高血圧・循環制御研究会
  • Place of Presentation: ホテル日航福岡
• [Remarks]
  • URL: http://www.med.oita-u.ac.jp/pathophysiology/
• [Remarks] 大分大学医学部病態生理学講座
  • URL: http://www.med.oita-u.ac.jp/pathophysiology/