A targeted disruption in connexin40 leads to distinct atrioventricular conduction defects

LM Bevilacqua, AM Simon, CT Maguire… - Journal of interventional …, 2000 - Springer
LM Bevilacqua, AM Simon, CT Maguire, J Gehrmann, H Wakimoto, DL Paul, CI Berul
Journal of interventional cardiac electrophysiology, 2000Springer
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) …
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.
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