Regulation of microRNAs responsible for ion channel remodeling in atrial fibrillation

• Project/Area Number: 25460292
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General physiology
• Research Institution: Oita University
• Principal Investigator: Ono Katsushige 大分大学, 医学部, 教授 (40253778)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: ion channel / electrophysiology / remodeling / atrial fibrillation / 心房細動 / リモデリング / microRNA / IK.ACh / カルシウム過負荷 / ヒト心筋 / イオンチャネル / マクロRNA / マイクロRNA

Outline of Final Research Achievements

Atrial fibrillation (AF) begets AF in part due to atrial remodeling. This study was to identify microRNA(s) responsible for electrical remodeling in AF. We identified 39 microRNAs differentially expressed in AF patient’s atria, including miR-30d as a candidate responsible for ion channel remodeling by in silico analysis. MiR-30d was significantly up-regulated in cardiomyocytes from AF patients, whereas the mRNA and protein levels of CACNA1C/Cav1.2 and KCNJ3/Kir3.1, postulated targets of miR-30d, were markedly reduced. KCNJ3/Kir3.1 expression was down-regulated by transfection of miR-30 precursor, concomitant with a reduction of the acetylcholine-sensitive inward-rectifier K+ current (IK.ACh). KCNJ3/Kir3.1 expression was enhanced by the knockdown of miR-30d. The downward remodeling of IK.ACh is attributed, at least in part, to deranged Ca2+ handling, leading to the up-regulation of miR-30d in human AF, revealing a novel post-transcriptional regulation of IK.ACh.

Research Products

• [Journal Article] Atrial fibrillation-mediated up-regulation of miR-30d regulates myocardial electrical remodeling of G-protein-gated K+ channel, IK.ACh (2016)
  • Author(s): Masaki Morishima, Eriko Iwata, Chisato Nakada, Yoshiyuki Tsukamoto, Hiroki Takanari, Shinji Miyamoto,Masatsugu Moriyama,Katsushige Ono
  • Journal Title: Circulation Journal Volume: 印刷中
  • NAID: 130005153582
  • Peer Reviewed / Acknowledgement Compliant
• [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: 22 Issue: 2 Pages: 87-93
  • DOI: 10.1016/j.pathophys.2015.01.002
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Short- and long-term inhibition of cardiac inward-rectifier potassium channel current by an antiarrhythmic drug bepridil (2015)
  • Author(s): Ma F, Takanari H, Masuda K, Morishima M, Ono K
  • Journal Title: Heart and Vessels Volume: 印刷中 Issue: 7 Pages: 1176-1184
  • DOI: 10.1007/s00380-015-0762-1
  • Peer Reviewed / Open Access
• [Presentation] MicroRNA-dependent regulation of K+ channel remodceling in human cardiomyocytes with persistent atrial fibrillation (2014)
  • Author(s): 森島真幸
  • Organizer: 第31回日本心電学会
  • Place of Presentation: 東京
  • Year and Date: 2014-07-22 – 2014-07-25
• [Presentation] Micro RNA-dependent regulation of K+ channel remodeling in (2014)
  • Author(s): 森島真幸
  • Organizer: 第31回日本心電学会学術集会
  • Place of Presentation: ザ・プリンスパークタワー東京（東京都港区）
• [Book] シンプル循環器学 (2015)
  • Author(s): 小野克重
  • Total Pages: 447
  • Publisher: 南江堂