Connexin-43 redistribution and gap junction activation during forced restraint protects against sudden arrhythmic death in rats.
BACKGROUND
Connexin-43 (Cx43) expression is reduced or redistributed in heart disease. Restraint or other emotional stressors might cause sudden death in persons with such diseases, but the mechanism of death and its connection to Cx43 during restraint remain unknown. Whether Cx43 distribution or gap junction (GJ) function during restraint is involved in sudden arrhythmic death in rats is addressed in this study.


RESULTS
Male Sprague-Dawley rats underwent immobilization (IMO), and individual electrocardiographic responses were monitored by telemetry. Heart sections were used to examine ventricular Cx43 distribution, and GJ intercellular communication (GJIC) activity was assessed using a dye-transfer assay. IMO induced the translocation of Cx43 into to the GJ-rich fraction, with a peak at 60 min. During IMO, Cx43 immunofluorescence was enhanced at intercalated discs, in association with GJIC activation, and premature ventricular contractions (PVCs) increased. In the presence of the GJ inhibitor, carbenoxolone (0.25 mg.kg(-1).h(-1)), IMO induced lethal ventricular tachycardia or fibrillation in 21.7% of rats, in association with QRS prolongation and increased PVCs.


CONCLUSIONS
IMO causes Cx43 translocation to intercalated discs, thereby reducing vulnerability to lethal arrhythmias via enhancing GJ coupling.
Unuma
Kana
K
Department of Forensic Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
Shintani-Ishida
Kaori
K
Tsushima
Kensuke
K
Shimosawa
Tatsuo
T
Ueyama
Takashi
T
Kuwahara
Masayoshi
M
Yoshida
Ken-ichi
K
D000818:Animals; D018031:Connexin 43 / Q000032:analysis / Q000378:metabolism*; D003645:Death, Sudden / Q000209:etiology*; D017629:Gap Junctions / Q000378:metabolism*; D008297:Male; D020011:Protective Agents; D021381:Protein Transport; D051381:Rats; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical / Q000009:adverse effects*; D014018:Tissue Distribution; D014693:Ventricular Fibrillation / Q000209:etiology
D018031:Connexin 43; D020011:Protective Agents