A targeted disruption in connexin40 leads to distinct atrioventricular conduction defects

J Interv Card Electrophysiol. 2000 Oct;4(3):459-67. doi: 10.1023/a:1009800328836.


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 electrophysiology (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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Atrioventricular Node / physiopathology*
  • Connexins / deficiency*
  • Electric Stimulation
  • Electrocardiography
  • Electrodes
  • Electrophysiology
  • Gap Junctions / metabolism*
  • Heart Rate
  • Mice
  • Mice, Inbred Strains
  • Mice, Knockout
  • Mice, Mutant Strains
  • Models, Animal
  • Probability
  • Reference Values
  • Statistics, Nonparametric
  • Tachycardia, Ventricular / diagnosis
  • Tachycardia, Ventricular / etiology
  • Tachycardia, Ventricular / physiopathology*


  • Connexins
  • connexin 40