title: Normal impulse propagation in the atrioventricular conduction system of Cx30.2/Cx40 double deficient mice.
abstract: Connexin (Cx) 30.2, Cx40 and Cx45 containing gap junctional channels contribute to electrical impulse propagation through the mouse atrioventricular node (AV-node). The cross talk in between these Cxs may be of great importance for AV-nodal conduction. We generated Cx30.2/Cx40 double deficient mice (Cx30.2(LacZ/LacZ)Cx40(-/-)) and analyzed the relative impact of Cx30.2 and Cx40 on cardiac conductive properties in vivo by use of electrophysiological examination. Cx30.2(LacZ/LacZ)Cx40(-/-) mice exhibited neither obvious cardiac malformations nor impaired contractile function. In surface-ECG analyses, Cx30.2(LacZ/LacZ)Cx40(-/-) and Cx40 deficient animals (Cx40(-/-)) showed significantly longer P-wave durations, PQ-intervals and prolonged QRS-complexes relative to wildtype littermates (WT). Cx30.2-deficient mice (Cx30.2(LacZ/LacZ)) developed shorter PQ-intervals as compared to WT, Cx40(-/-) or Cx30.2/Cx40 double deficient mice. Intracardiac evaluation of the atria-His (AH) and His-ventricle (HV) intervals representing supra and infra-Hisian conduction yielded significant acceleration of supra-Hisian conductivity in Cx30.2(LacZ/LacZ) (AH: 28.2+/-4.3 ms) and prolongation of infra-Hisian conduction in Cx40(-/-) mice (HV: 13.7+/-2.6 ms). These parameters were unchanged in the Cx30.2(LacZ/LacZ)Cx40(-/-) mice (AH: 37.3+/-5.5 ms, HV: 11.7+/-2.6 ms), which exhibited AV-nodal and ventricular conduction times similar to WT animals (AH: 35.9+/-4.4 ms, HV: 10.5+/-1.9 ms). We conclude that the remaining Cx45 gap junctional channels are sufficient to maintain electrical coupling and cardiac impulse propagation in the AV-node and proximal ventricular conduction system in mice. We suggest that Cx30.2 and Cx40 act as counterparts in the AV-node and His-bundle, decreasing or increasing, respectively, electrical coupling and conduction velocity in these areas.
authors.affiliation: Department of Medicine Cardiology, University of Bonn, Sigmund-Freud Strasse 25, D-53105 Bonn, Germany. jan.schrickel@ukb.uni-bonn.de
authors.forename: Jan W
authors.initials: JW
authors.lastname: Schrickel
authors.forename: Maria M
authors.initials: MM
authors.lastname: Kreuzberg
authors.forename: Alexander
authors.initials: A
authors.lastname: Ghanem
authors.forename: Jung-Sun
authors.initials: JS
authors.lastname: Kim
authors.forename: Markus
authors.initials: M
authors.lastname: Linhart
authors.forename: Rene
authors.initials: R
authors.lastname: Andrié
authors.forename: Klaus
authors.initials: K
authors.lastname: Tiemann
authors.forename: Georg
authors.initials: G
authors.lastname: Nickenig
authors.forename: Thorsten
authors.initials: T
authors.lastname: Lewalter
authors.forename: Klaus
authors.initials: K
authors.lastname: Willecke
mesh_terms: D000818:Animals; D001281:Atrial Fibrillation / Q000000981:diagnostic imaging / Q000503:physiopathology; D001283:Atrioventricular Node / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D017630:Connexins / Q000172:deficiency* / Q000378:metabolism; D004452:Echocardiography; D055724:Electrophysiological Phenomena; D006329:Heart Conduction System / Q000378:metabolism / Q000502:physiology*; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D010641:Phenotype; D000097003:Gap Junction alpha-5 Protein
chemical_list: D017630:Connexins; D000097003:Gap Junction alpha-5 Protein; C510757:connexin 30.2, mouse