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

INTRODUCTION: Previous electrophysiologic investigations have described AV conduction disturbances in connexin40 (Cx40)-deficient mice. Because expression of 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-Purkinje 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 deficiencies 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.