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.
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-deficientmice, including longer PR, AH, and HV intervals, increased AV refractory periods, and increased AV Wenckebach and 2:1 block cycle lengths. Connexin40-deficientmice 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.
Authors: S A Thomas; R B Schuessler; C I Berul; M A Beardslee; E C Beyer; M E Mendelsohn; J E Saffitz Journal: Circulation Date: 1998-02-24 Impact factor: 29.690
Authors: D Gros; T Jarry-Guichard; I Ten Velde; A de Maziere; M J van Kempen; J Davoust; J P Briand; A F Moorman; H J Jongsma Journal: Circ Res Date: 1994-05 Impact factor: 17.367
Authors: H M van der Velden; M J van Kempen; M C Wijffels; M van Zijverden; W A Groenewegen; M A Allessie; H J Jongsma Journal: J Cardiovasc Electrophysiol Date: 1998-06
Authors: David E Arnolds; Fang Liu; John P Fahrenbach; Gene H Kim; Kurt J Schillinger; Scott Smemo; Elizabeth M McNally; Marcelo A Nobrega; Vickas V Patel; Ivan P Moskowitz Journal: J Clin Invest Date: 2012-06-25 Impact factor: 14.808
Authors: Shan-Shan Zhang; Kyoung-Han Kim; Anna Rosen; James W Smyth; Rui Sakuma; Paul Delgado-Olguín; Mark Davis; Neil C Chi; Vijitha Puviindran; Nathalie Gaborit; Tatyana Sukonnik; John N Wylie; Koroboshka Brand-Arzamendi; Gerrie P Farman; Jieun Kim; Robert A Rose; Phillip A Marsden; Yonghong Zhu; Yu-Qing Zhou; Lucile Miquerol; R Mark Henkelman; Didier Y R Stainier; Robin M Shaw; Chi-chung Hui; Benoit G Bruneau; Peter H Backx Journal: Proc Natl Acad Sci U S A Date: 2011-08-08 Impact factor: 11.205
Authors: Ramesh S Yadava; Qing Yu; Mahua Mandal; Frank Rigo; C Frank Bennett; Mani S Mahadevan Journal: Hum Mol Genet Date: 2020-06-03 Impact factor: 6.150