Conduction Disturbances and Increased Atrial Vulnerability in Connexin40-Deficient Mice Analyzed by Transesophageal Stimulation

Abstract

Background —Recently, it has been reported that connexin40 (Cx40) deficiency in targeted mouse mutants is associated with a prolongation of P-wave and QRS complex duration on surface electrograms. The specific effects of Cx40 deficiency on sinus node function, sinoatrial, and atrioventricular conduction properties as well as on atrial vulnerability have not yet been investigated systematically by electrophysiological analysis. Methods and Results —Fifty-two mice (18 Cx40 +/+ , 15 Cx40 +/− , and 19 Cx40 −/− mice) were subjected to rapid atrial transesophageal stimulation after anesthesia with avertin. A significant prolongation of sinus node recovery time was noticed in Cx40 −/− mice compared with Cx40 +/− and Cx40 +/+ mice (287.8±109.0 vs 211.1±61.8 vs 204.4±60.9 ms; P <0.05). In addition, Wenckebach periodicity occurred at significantly longer atrial pacing cycle lengths in Cx40 −/− mice than in Cx40 +/− or Cx40 +/+ mice (93.3±11.8 vs 83.9±9.7 vs 82.8±8.0 ms, P <0.05). Analysis of 27 Cx40 −/− mice showed a significant increase in intra-atrial conduction time and atrioventricular conduction time compared with 52 Cx40 +/− and 31 wild-type (Cx40 +/+ ) mice. Furthermore, in Cx40 −/− mice, atrial tachyarrhythmias could be induced frequently by atrial burst pacing, whereas no atrial arrhythmias were inducible in heterozygous or wild-type mice. Conclusions —This study demonstrates that Cx40 deficiency is associated with sinoatrial, intra-atrial, and atrioventricular conduction disturbances. In atrial myocardium of the mouse, Cx40 deficiency results in increased atrial vulnerability and might contribute to arrhythmogenesis.