Increased susceptibility to ischemia-induced ventricular tachyarrhythmias in depressed rats: Involvement of reduction of connexin 43

Abstract

Connexin 43 (Cx43) has been reported to contribute to the occurrence of ventricular arrhythmias during myocardial ischemia (MI). In this study, we investigated the expression of Cx43 and the incidences of ventricular tachyarrhythmias [i.e., ventricular tachycardia (VT) and ventricular fibrillation (VF)] during acute MI in chronic mild stress (CMS) in rats. Male Sprague-Dawley (SD) control and CMS rats were assigned into a sham operation (SO) group and a MI group. Ventricular tachyarrhythmias were assessed and Cx43 protein expression was measured by Western blotting. During 30-min ischemia, the incidences of VT (7/12, 58.3%) and VF (5/12, 41.7%) in the CMS-MI group were significantly decreased compared with those in the control-MI group (12/12, 100.0% and 11/12, 91.7%; P<0.05). The amount of total Cx43 of the CMS-SO group was significantly decreased to approximately 50% compared with that of the control-SO group (P<0.05). The 30-min ischemia did not result in a significant change in the amount of total Cx43 (total Cx43 is defined as the non-phosphorylated Cx43 and phosphorylated Cx43) compared to that of the SO group in CMS rats (P>0.05). The amount of non-phosphorylated Cx43 in the CMS-MI group was markedly increased compared to that of the CMS-SO group (P<0.05), suggesting that the relative amount of phosphorylated Cx43 was significantly decreased in CMS rats. The gap junctional permeability in the CMS-MI group (50.4±4.9%) was significantly decreased compared with the normal non-ischemic value in the CMS-SO group (100%). The present study suggested that the incidence of ischemia-induced ventricular tachyarrhythmias was markedly increased in depressed rats, which may be associated with the reduction of Cx43 protein expression in the ventricle of depressed rats.