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.