Restraint Stress Induces Connexin-43 Translocation via α-Adrenoceptors in Rat Heart

• Unuma Kana

  Department of Forensic Medicine, Graduate School of Medicine, University of Tokyo Research Fellow of the Japan Society for the Promotion of Science (JSPS), University of Tokyo Hospital

• Shintani-Ishida Kaori

  Department of Forensic Medicine, Graduate School of Medicine, University of Tokyo

• Yahagi Naoki

  Department of Emergency and Critical Care Medicine, University of Tokyo Hospital

• Tsushima Kensuke

  Department of Cardiovascular Medicine, University of Tokyo Hospital

• Shimosawa Tatsuo

  Department of Clinical Laboratory, University of Tokyo Hospital

• Ueyama Takashi

  Departments of Anatomy and Cell Biology, Wakayama Medical University

• Yoshida Ken-ichi

  Department of Forensic Medicine, Graduate School of Medicine, University of Tokyo

Bibliographic Information

Other Title

• Restraint Stress Induces Connexin-43 Translocation via α-Adrenoceptors in Rat Heart

Abstract

Background: Immobilization (IMO) confers emotional stress in animals and humans. It was recently reported that IMO in rats induced translocation of connexin-43 (Cx43) to gap junctions (GJs) and attenuated arrhythmogenesis with GJ inhibition, and Cx43 translocation in the ischemic heart was also shown. Few reports show the contribution of adrenoceptors to Cx43 upregulation in cardiomyocytes, but the involvement of adrenoceptors and ischemia in Cx43 translocation in IMO remains elusive. Methods and Results: Male Sprague-Dawley rats underwent IMO and the ventricular distribution of Cx43 was examined by western blotting. IMO induced translocation of Cx43 to the GJ-enriched membrane fraction, with a peak at 60min. The IMO-induced Cx43 translocation was inhibited by pretreatment with the α₁-adrenoceptor blockers, prazosin (1mg/kg, PO) and bunazosin (4mg/kg, PO), but not with either the β₁-blocker, metoprolol (10mg/kg, IP), or the β₁₊₂-blocker, propranolol (1mg/kg, PO). The translocation was inhibited by the nitric oxide, donor isosorbide dinitrate (100μg·kg^-1·min^-1, IV), possibly through sympathetic inhibition. Hypoxia inducible factor-1α was not redistributed by IMO. The β-blockers, but not the α-blockers, inhibited the premature ventricular contractions (PVCs) induced by IMO. Conclusions: Translocation of Cx43 to the GJ-enriched fraction occurs via the α₁-adrenoceptor pathway, independently of ischemia. The β-adrenoceptor pathway contributes to the inducing of PVCs in IMO. (Circ J 2010; 74: 2693-2701)<br>

Journal

• Circulation Journal

  Circulation Journal 74 (12), 2693-2701, 2010

  The Japanese Circulation Society

Keywords

• α-/β-adrenoceptor
• Arrhythmia
• β-blocker
• Connexin-43
• Emotional stress

Details

• CRID: 1390282680081540608
• NII Article ID: 10027424654
• NII Book ID: AA11591968
• DOI: 10.1253/circj.cj-10-0529
• ISSN: 13474820
• ISSN: 13469843
• Web Site: https://www.jstage.jst.go.jp/article/circj/74/12/74_CJ-10-0529/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2011132870
• Text Lang: en
• Data Source:
  • JaLC
  • Crossref
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed