title: A targeted disruption in connexin40 leads to distinct atrioventricular conduction defects.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Cardiology, Children's Hospital, Harvard Medical School Boston, Massachusetts 02115, USA.
authors.forename: L M
authors.initials: LM
authors.lastname: Bevilacqua
authors.forename: A M
authors.initials: AM
authors.lastname: Simon
authors.forename: C T
authors.initials: CT
authors.lastname: Maguire
authors.forename: J
authors.initials: J
authors.lastname: Gehrmann
authors.forename: H
authors.initials: H
authors.lastname: Wakimoto
authors.forename: D L
authors.initials: DL
authors.lastname: Paul
authors.forename: C I
authors.initials: CI
authors.lastname: Berul
mesh_terms: D000818:Animals; D001283:Atrioventricular Node / Q000503:physiopathology*; D017630:Connexins / Q000172:deficiency*; D004558:Electric Stimulation; D004562:Electrocardiography; D004566:Electrodes; D004594:Electrophysiology; D017629:Gap Junctions / Q000378:metabolism*; D006339:Heart Rate; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D023421:Models, Animal; D011336:Probability; D012016:Reference Values; D018709:Statistics, Nonparametric; D017180:Tachycardia, Ventricular / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology*; D000097003:Gap Junction alpha-5 Protein
chemical_list: D017630:Connexins; D000097003:Gap Junction alpha-5 Protein