Abstract 501: Function of Connexin30.2 and Connexin40 in AV-Nodal Conduction
Objective: Connexin30.2 (Cx30.2) and Connexin40 (Cx40) have been shown to be major components of the gap-junctions murine AV-nodal tissue. Cx30.2 has been shown to contribute to physiological conduction slowing of the AV-node but functional interactions of Cx30.2 and fast conducting connexins like Cx40 in the AV-node remaines unclear.
Methods: 18 wildtype-(WT), 10 Cx30.2-deficient (Cx30.2−/−), 6 Cx40-deficient (Cx40−/−) and 10 Cx30.2/Cx40 double-deficient (Cx30.2/Cx40−/−) mice were in vivo electrophysiologically investigated using transvenous right cardiac catheterization.
Results: Independent from a tendency towards P-wave prolongation in Cx40−/− and Cx30.2/Cx40−/− mice, PQ was significantly shorter in Cx30.2 (35.7±3.4 ms) as compared to all other investigated groups (WT: 46.6±4.0 ms; Cx40−/−: 50.8±6.2 ms; Cx30.2/Cx40−/−: 51.6±5.1 ms; p<0.0001). Accelerated AV-conduction was attributable to a significant faster supra-Hisian conductivity with shortened AH-intervals in Cx30.2−/− (28.2±4.3 ms vs. WT: 35.9±4.4 ms; Cx40−/−: 35.8±1.9 ms; Cx30.2/Cx40−/−: 37.3±5.5 ms, p<0.0001). A significantly lower Wenckebach-periodicity was present in Cx30.2−/− (basal stimulation cycle-length S1S1: 79.7±7.2 ms), but not in Cx30.2/Cx40−/−(81.5±6.7 ms; p<0.001) compared to the other groups. The HV-Interval was prolonged in Cx40−/− compared to WT and Cx30.2−/− as an indicator for impaired infra-Hisian conductivity. As a result, QRS was prolonged in Cx40−/− (21.3±2.7 ms) and Cx30.2/Cx40−/−(19.9±2.4 ms) compared WT (12.9±1.9 ms) and Cx30.2−/− (14.2±2.0 ms; p<0.0001).
Conclusions: Thefact that no acceleration of AV-nodal conduction is present in Cx30.2/Cx40−/− compared to Cx30.2−/− implicates that the presence of fast conducting Cx40 is essential for faster impulse propagation in Cx30.2−/−. This study strongly points towards functional interactions of Cx40 and slow conducting Cx30.2 in the murine AV-node. The conductive properties of the AV-node under physiological conditions and in pathological states (such as hereditary AV-blocks and AV-nodal reentrant tachycardia) might therefore be mediated by a differential expression or activation of such interacting connexins.