Connexin40‐Deficient Mice Exhibit Atrioventricular Nodal and Infra‐Hisian Conduction Abnormalities

AV Nodal and Infra‐Hisian Conduction in Cx40 Mice. Introduction: Previous electrophysiologic investigations have described AV conduction disturbances in connexin4(Cx40)‐deficient mice. Because expression or(Cx40 occurs predominantly in the atria and His‐Purkinje system of the mouse heart, the AV conduction disturbances were thought to be secondary to disruption in His‐Pnrkinje function. However, the lack of a His‐bundle electrogram recording in the mouse has limited further investigation of the importance of Cx40. Using a novel technique to record His‐bundle recordings in Cx40‐deficient mice, we define the physiologic importance of defciencies in Cx40. Methods and Results: Ten Cx40 ‐/‐ mice and 11 Cx40 +/+ controls underwent a blinded, in vivo, closed chest electrophysiology study at 9 to 12 weeks of age. In the Cx40 +/+ mice, the PR interval was significantly longer compared with Cx40 +/+ mice (44.6 ± 6.4 msec vs 36.0 ± 4.1 msec, P = 0.002). Not only the HV interval (14.0 ± 3.0 msec vs 10.4 ± 1.2 msec, P = 0.003) but also the AH interval (33.2 ± 4.8 msec vs 27.1 ± 3.7 msec, P = 0.006), AV Wenckebach cycle lengths, and AV nodal effective and functional refractory periods were prolonged in Cx40 ‐/‐ compared with Cx40 +/+ mice. Conclusion: Cx40‐deficient mice exhibit significant delay not only in infra‐Hisian conduction, as would be expected from the expression of Cx40 in the His‐Purkinje system but also in the electrophysiologic parameters that reflect AV nodal conduction. Our data suggest a significant role of Cx40 in atrionodal conduction and/or in proximal His‐bundle conduction,