Cardiac conduction abnormalities in mice lacking the gap junction protein connexin40

Introduction: The gap junction protein connexin40 (Cx40) normally is expres sed in the murine atrial myocardium and ventricular conduction system. In m ice lacking Cx40, several changes in the surface ECG have been described, I n this study, we analyzed cardiac conduction in more detail. Methods and Results: In open chest mice under urethane anesthesia, epicardi al electrodes were used to determine a number of atrial and ventricular pac ing parameters. The corrected sinus node recovery time was significantly lo nger 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(-/-) mic e compared with the wild type (84.6 +/- 5.4 msec vs 78.8 +/- 3.6 msec), wit h the AV node probably limiting AV conduction in both cases. Whereas arrhyt hmias could not be induced by ventricular burst pacing in any of the mice, atrial burst pacing induced atrial tachyarrhythmias in 5 of 10 Cx40(-/-) mi ce, but not in any of 9 Cx40(+/+) mice. Conduction velocities were measured in vivo using an array of unipolar recording electrodes. Ventricular condu ction velocity did not differ between the groups, hut atrial conduction vel ocity was reduced by 30% in Cx40-/- mice compared with the wild type. Heter ozygous Cx40(+/-) mice did not differ significantly from the wild type in a ny respect. Conclusion: These findings indicate that in the atria and the AV conduction system, Cx40 is an important determinant of conduction.