Myocardial Connexin 43 downregulation during physical exercise

TISCORNIA G.; MORETTA R; ARGENZIANO M.; AMORENA C.; GARCÍA-GRAS E.

Niza

Congreso; Congreso Bi-anual de la Sociedad Europea de Cardiologia (Cardiostim); 2010

Sociedad Europea de Cardiologia

In individuals suffering from certain cardiomyopathies  (ARVC, HC, etc), intense physical exercise can trigger arrhythmic events. The  molecular mechanism that generates such arrhythmogenic substrate is unknown. In  mice models inhibition of Connexin 43 expression is arrhythmogenic. Several  cardiomyopathies inhibit Connexin 43 expression per se. We hypothesized that  the mechanism responsible for physical exercise induced arrhythmogenesis could  be centred on an acute decrease in the expression of Connexin 43 in the ventricular  myocardium. We used untrained and swim trained mice in our experiments. We  evaluated the effect of swimming on the expression of Connexin 43 at the mRNA  and protein levels by semi-quantitative RT-PCR and western blot respectively.  In trained mice we found a 55% inhibition of Connexin 43 mRNA after exercising  15`. Connexin 43 protein suffers a 50% inhibition starting at minute 60`. The  levels of inhibition are sustained in time and the recovery of Connexin 43  expression, after the exercise is finished takes up to 60`. In untrained mice  we only observed mRNA expression inhibition beginning after 90` of exercise.  Propranolol prevents exercise induced Connexin 43 expression inhibition  indicating a central role for sympathetic stimulation. Conclusion: We report a  mechanism that could explain the occurrence of arrhythmogenic events in  susceptible individuals during and up to one hour after a session of physical  exercise.