Cardiac Conduction Abnormalities in Mice Lacking the Gap Junction Protein Connexin40

INTRODUCTION: The gap junction protein connexin40 (Cx40) normally is expressed in the murine atrial myocardium and ventricular conduction system. In mice lacking Cx40, several changes in the surface ECG have been described. In this study, we analyzed cardiac conduction in more detail. METHODS AND RESULTS: In open chest mice under urethane anesthesia, epicardial electrodes were used to determine a number of atrial and ventricular pacing parameters. The corrected sinus node recovery time was significantly longer in Cx40-/- mice than in Cx40+/+ mice (44.4 +/- 7.2 msec vs 35.5 +/- 8.0 msec). In addition, the Wenckebach period was longer in Cx40-/- mice compared with the wild type (84.6 +/- 5.4 msec vs 78.8 +/- 3.6 msec), with the AV node probably limiting AV conduction in both cases. Whereas arrhythmias could not be induced by ventricular burst pacing in any of the mice, atrial burst pacing induced atrial tachyarrhythmias in 5 of 10 Cx40-/- mice, but not in any of 9 Cx40+/+ mice. Conduction velocities were measured in vivo using an array of unipolar recording electrodes. Ventricular conduction velocity did not differ between the groups, but atrial conduction velocity was reduced by 30% in Cx40-/- mice compared with the wild type. Heterozygous Cx40+/- mice did not differ significantly from the wild type in any respect. CONCLUSION: These findings indicate that in the atria and the AV conduction system, Cx40 is an important determinant of conduction.