Journal of Interventional Cardiac Electrophysiology

, Volume 4, Issue 3, pp 459–567

A Targeted Disruption in Connexin40 Leads to Distinct Atrioventricular Conduction Defects

Authors

  • Laura M. Bevilacqua
    • Department of CardiologyChildren's Hospital, Harvard Medical School Boston
  • Alexander M. Simon
    • Department of NeurobiologyHarvard Medical School
  • Colin T. Maguire
    • Department of CardiologyChildren's Hospital, Harvard Medical School Boston
  • Josef Gehrmann
    • Department of CardiologyChildren's Hospital, Harvard Medical School Boston
  • Hiroko Wakimoto
    • Department of CardiologyChildren's Hospital, Harvard Medical School Boston
  • David L. Paul
    • Department of NeurobiologyHarvard Medical School
  • Charles I. Berul
    • Department of CardiologyChildren's Hospital, Harvard Medical School Boston
Article

DOI: 10.1023/A:1009800328836

Cite this article as:
Bevilacqua, L.M., Simon, A.M., Maguire, C.T. et al. J Interv Card Electrophysiol (2000) 4: 459. doi:10.1023/A:1009800328836

Abstract

Introduction: Gap junctions consist of connexin (Cx) proteins that enable electrical coupling of adjacent cells and propagation of action potentials. Cx40 is solely expressed in the atrium and His-Purkinje system. The purpose of this study was to evaluate atrioventricular (AV) conduction in mice with a homozygous deletion of Connexin40 (Cx40−/−).

Methods: Surface ECGs, intracardiac electrophysi-ology (EP) studies, and ambulatory telemetry were performed in Cx40−/− mutant mice and wild-type (WT) controls. Atrioventricular (AV) conduction parameters and arrhythmia inducibility were evaluated using programmed stimulation. Analysis of heart rate variability was based on results of ambulatory monitoring.

Results: Significant findings included prolonged measures of AV refractoriness and conduction in connexin40-deficient mice, including longer PR, AH, and HV intervals, increased AV refractory periods, and increased AV Wenckebach and 2:1 block cycle lengths. Connexin40-deficient mice also had an increased incidence of inducible ventricular tachycardia, decreased basal heart rates, and increased heart rate variability.

Conclusion: A homozygous disruption of Cx40 results in prolonged AV conduction parameters due to abnormal electrical coupling in the specialized conduction system, which may also predispose to arrhythmia vulnerability.

animal modelselectrophysiologyarrhythmiasconnexingap junction
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© Kluwer Academic Publishers 2000