Abstract 8470: Conditional Deletion of Cardiac Connexin45 Results in Impaired Av-Nodal Conduction Properties
Introduction: Cx45 has been proposed to maintain basal AV-nodal conduction. The exact function of Cx45 in the adult heart has not yet been identified as Cx45 deficient mice are embryonic lethal.
Methods: We generated a transgenic mouse line by breeding floxed Cx45 mice with inducible cardiomyocyte-specific Cre-recombinase-expressing mice. Cardiac Cx45 was conditionally deleted by intraperitoneal administration of tamoxifen in adult mice (Cx45 fl/fl:aMHC-CreERt2). In these mice and control littermates (Cx45 fl/fl), we performed telemetric ECGs (n=5) and in vivo electrophysiological investigations (EPI) using transvenous catheterization to assess standard EPI-parameters (n=10).
Results: Holter ECGs showed similar heart rates in the genotypes (590±65 in Cx45 fl/fl:aMHC-CreERt2 vs. 571±72 in Cx45 fl/fl). PQ-intervals were prolonged in Cx45 fl/fl:aMHC-CreERt2 (41.0±2.2ms vs. 36.4±3.1ms; p<0.05) and the P-wave was shorter (8.9±1.6ms vs. 6.6±1.0ms; p<0.05). Under inhalative ansthesia, heart rate was significantly lower in both genotypes (382±43 in Cx45 fl/fl:aMHC-CreERt2; 419±10 in Cx45 fl/fl; p<0.05 vs. spontaneous heart rate), but PQ remained significantly prolonged in the conditional knock-out mice (41.2±4.7ms vs. 37.5±3.5ms; p<0.05). Evaluation of intracardiac electrograms showed no measurable alterations of supra- or infra-Hisian conduction at comparable AH- and HV-intervals. Sinus-nodal recovery period and Wenckebach periodicity were not significantly different among the groups.
Conclusions: Our mouse mutants with conditional cardiac deletion of Cx45 represent the first model for evaluation of Cx45 function in the adult heart. Our data show prolonged AV-intervals and no impaired AV-nodal conduction under fast heart rates. These findings support the thesis of Cx45 as a provider of basal AV-nodal conductivity, potentially as a backup system for maintaining AV-nodal conduction under pathological conditions, but with minor importance for AV-nodal conductivity when Cx30.2 and Cx40 are present.
- © 2011 by American Heart Association, Inc.