Short-term pacing in the mouse alters cardiac expression of connexin43.
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.
Kontogeorgis
Andrianos
A
Leon H, Charney Division of Cardiology, Department of Medicine, New York University School of Medicine, New York, NY, USA. a.kontogeorgis@imperial.ac.uk
Kaba
Riyaz A
RA
Kang
Eunice
E
Feig
Jonathan E
JE
Gupta
Pritha P
PP
Ponzio
Marc
M
Liu
Fangyu
F
Rindler
Michael J
MJ
Wit
Andrew L
AL
Fisher
Edward A
EA
Peters
Nicholas S
NS
Gutstein
David E
DE
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
D018031:Connexin 43