Abstract

Recent studies suggest that cadherin-mediated adherens junctions may be impaired in diseases and pathologic processes related to ventricular arrhythmias, which are concomitant with decreased connexin 43 (Cx43). In this study, we evaluated the acute arrhythmogenic effects of adherens junction impairment in isolated rat hearts. A total of 56 hearts isolated from adult male rats were perfused with 0.2 mM AHAVD, a synthetic peptide that specifically inhibits N-cadherin (n = 18); 0.2 mM IPPINL, a nonsense peptidase that contains the highly conserved cadherin sequence (n = 18), and oxygenated Krebs–Henseleit buffer as the control (n = 20). Under programmed stimuli, ventricular tachyarrhythmias were induced more in the AHAVD-perfused hearts (9/18) than the IPPINL-perfused hearts (4/18) and those in the control (3/20) group (P < 0.05). The conduction velocity of the left ventricular myocardium exhibited an inverse pattern in these three groups (53.5 ± 6.3 cm/s, 65.2 ± 6.2 cm/s, and 66.3 ± 8.8 cm/s, respectively, P < 0.05). The effective refractory period and the epicardial action potential duration at 90% repolarization were not significantly different among the groups after 1 h of perfusion. Cx43 redistribution and PS368 decrease was observed in the AHAVD-perfused heart tissues. The reduction in functional GJs in the intercalated discs of cardiomyocytes may be one of the initial mechanisms by which myocardial conduction is blunted. Furthermore, rat hearts with impaired adherens junctions are more susceptible to ventricular tachyarrhythmias.

Key words: Adherens junctions, N-cadherin, connexin 43, pS368, Ventricular tachyarrhythmia.