Connexin45 Provides Optimal AV-Nodal Conduction in the Adult Mouse Heart
Rationale: The gap junctional protein Connexin45 (Cx45) is strongly expressed in the early embryonic myocardium. In the adult heart of mouse and man the expression is mainly restricted to the cardiac conduction system. Cx45 plays an essential role for development and function of the embryonic heart because general and cardiomyocyte-directed deficiencies of Cx45 in mice lead to embryonic lethality due to morphological and functional cardiovascular defects. The function of Cx45 in the adult mouse has not yet been cleared.
Objective: To clarify the function of Cx45 in the adult mouse heart.
Methods and Results: In order to circumvent the embryonic lethality resulting from Cx45 deficiency, mice were generated in which deletion of Cx45 was specifically induced in cardiomyocytes of adult mice. These Cx45-deficient mice were viable but showed a decrease in atrioventricular (AV)-nodal conductivity. In addition, the Connexin30.2 (Cx30.2) protein which is coexpressed with Cx45 in the cardiac conduction system was posttranscriptionally reduced by 70% in mutant hearts. Furthermore, deletion of both Cx45 and Cx30.2 resulted in viable mice that, however, showed stronger impairment of AV-nodal conduction than the single Cx45-deficient mice.
Conclusions: Cx45 is required for optimal impulse propagation in the AV node and stabilizes the level of the coexpressed Cx30.2 protein in the adult mouse heart. In contrast to the embryo, Cx45 is not essential for viability of adult mice.
- Cardiac gap junction connexins
- Conduction velocity
- Gap junctions
- Transgenic mice
- Connexin 45
- Connexin 30.2
- atrioventricular node
- Received April 2, 2012.
- Accepted September 14, 2012.
- Copyright © 2012, American Heart Association