Connexin45 provides optimal atrioventricular nodal conduction in the adult mouse heart

Marina Frank, Angela Wirth, René P. Andrié, Maria M. Kreuzberg, Radoslaw Dobrowolski, Gerald Seifert, Stefan Offermanns, Georg Nickenig, Klaus Willecke, Jan W. Schrickel

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

RATIONALE: The gap junctional protein connexin (Cx) 45 is strongly expressed in the early embryonic myocardium. In the adult hearts of mice and humans, the expression mainly is 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 attributable 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: To circumvent the embryonic lethality resulting from Cx45 deficiency, mice were generated in which deletion of Cx45 specifically was induced in cardiomyocytes of adult mice. These Cx45-deficient mice were viable but showed a decrease in atrioventricular nodal conductivity. In addition, the Cx30.2 protein that 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 atrioventricular nodal conduction than the single Cx45-deficient mice. CONCLUSIONS: Cx45 is required for optimal impulse propagation in the atrioventricular 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 the viability of adult mice.

Original languageEnglish (US)
Pages (from-to)1528-1538
Number of pages11
JournalCirculation research
Volume111
Issue number12
DOIs
StatePublished - Dec 2012

Keywords

  • adult mouse heart
  • atrioventricular node
  • conduction velocity
  • connexin30.2
  • connexin45
  • gap junction

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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