Restraint stress induces connexin-43 translocation via α-adrenoceptors in rat heart.
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.


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 α(1)-adrenoceptor blockers, prazosin (1mg/kg, PO) and bunazosin (4mg/kg, PO), but not with either the β(1)-blocker, metoprolol (10mg/kg, IP), or the β(1+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 α(1)-adrenoceptor pathway, independently of ischemia. The β-adrenoceptor pathway contributes to the inducing of PVCs in IMO.
Unuma
Kana
K
Department of Forensic Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
Shintani-Ishida
Kaori
K
Yahagi
Naoki
N
Tsushima
Kensuke
K
Shimosawa
Tatsuo
T
Ueyama
Takashi
T
Yoshida
Ken-ichi
K
D058668:Adrenergic alpha-1 Receptor Antagonists / Q000494:pharmacology; D058671:Adrenergic beta-1 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D018031:Connexin 43 / Q000378:metabolism*; D017629:Gap Junctions / Q000378:metabolism*; D007548:Isosorbide Dinitrate / Q000494:pharmacology; D008297:Male; D008790:Metoprolol / Q000494:pharmacology; D017202:Myocardial Ischemia / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D012149:Restraint, Physical; D013312:Stress, Physiological
D058668:Adrenergic alpha-1 Receptor Antagonists; D058671:Adrenergic beta-1 Receptor Antagonists; D018031:Connexin 43; D020030:Nitric Oxide Donors; D011942:Receptors, Adrenergic, alpha; D011433:Propranolol; D008790:Metoprolol; D007548:Isosorbide Dinitrate