title: Short-term pacing in the mouse alters cardiac expression of connexin43.
abstract: BACKGROUND
  Cardiac insults such as ischemia, infarction, hypertrophy and dilatation are often accompanied by altered abundance and/or localization of the connexin43 gap junction protein, which may predispose towards arrhythmic complications. Models of chronic dyssynchronous cardiac activation have also been shown to result in redistribution of connexin43 in cardiomyocytes. We hypothesized that alterations in connexin43 expression and localization in the mouse heart might be induced by ventricular pacing over a short period of time.
  
  
  RESULTS
  The subdiaphragmatic approach was used to pace a series of wild type mice for six hours before the hearts were removed for analysis. Mice were paced at 10-15% above their average anesthetized sinus rate and monitored to ensure 1:1 capture. Short-term pacing resulted in a significant reduction in connexin43 mRNA abundance, a partial redistribution of connexin43 from the sarcolemma to a non-sarcolemmal fraction, and accumulation of ubiquitinated connexin43 without a significant change in overall connexin43 protein levels. These early pacing-induced changes in connexin43 expression were not accompanied by decreased cardiac function, prolonged refractoriness or increased inducibility into sustained arrhythmias.
  
  
  CONCLUSIONS
  Our data suggest that short-term pacing is associated with incipient changes in the expression of the connexin43 gap junction, possibly including decreased production and a slowed rate of degradation. This murine model may facilitate the study of early molecular changes induced by pacing and may ultimately assist in the development of strategies to prevent gap junction remodeling and the associated arrhythmic complications of cardiac disease.
authors.affiliation: Leon H, Charney Division of Cardiology, Department of Medicine, New York University School of Medicine, New York, NY, USA. a.kontogeorgis@imperial.ac.uk
authors.forename: Andrianos
authors.initials: A
authors.lastname: Kontogeorgis
authors.forename: Riyaz A
authors.initials: RA
authors.lastname: Kaba
authors.forename: Eunice
authors.initials: E
authors.lastname: Kang
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Feig
authors.forename: Pritha P
authors.initials: PP
authors.lastname: Gupta
authors.forename: Marc
authors.initials: M
authors.lastname: Ponzio
authors.forename: Fangyu
authors.initials: F
authors.lastname: Liu
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Rindler
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Wit
authors.forename: Edward A
authors.initials: EA
authors.lastname: Fisher
authors.forename: Nicholas S
authors.initials: NS
authors.lastname: Peters
authors.forename: David E
authors.initials: DE
authors.lastname: Gutstein
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology; D000818:Animals; D002304:Cardiac Pacing, Artificial / Q000379:methods*; D018031:Connexin 43 / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D006329:Heart Conduction System / Q000502:physiology*; D006339:Heart Rate / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D018031:Connexin 43