title: Altered right atrial excitation and propagation in connexin40 knockout mice.
abstract: BACKGROUND
  Intercellular coupling via connexin40 (Cx40) gap junction channels is an important determinant of impulse propagation in the atria.
  
  
  RESULTS
  We studied the role of Cx40 in intra-atrial excitation and propagation in wild-type (Cx40(+/+)) and knockout (Cx40(-/-)) mice using high-resolution, dual-wavelength optical mapping. On ECG, the P wave was significantly prolonged in Cx40(-/-) mice (13.4+/-0.5 versus 11.4+/-0.3 ms in Cx40(+/+)). In Cx40(+/+) hearts, spontaneous right atrial (RA) activation showed a focal breakthrough at the junction of the right superior vena cava, sulcus terminalis, and RA free wall, corresponding to the location of the sinoatrial node. In contrast, Cx40(-/-) hearts displayed ectopic breakthrough sites at the base of the sulcus terminalis, RA free wall, and right superior vena cava. Progressive ablation of such sites in 4 Cx40(-/-) mice resulted in ectopic focus migration and cycle length prolongation. In all Cx40(-/-) hearts the focus ultimately shifted to the sinoatrial node at a very prolonged cycle length (initial ectopic cycle length, 182+/-20 ms; postablation sinus cycle length, 387+/-44 ms). In a second group of experiments, epicardial pacing at 10 Hz revealed slower conduction in the RA free wall of 5 Cx40(-/-) hearts than in 5 Cx40(+/+) hearts (0.61+/-0.07 versus 0.94+/-0.07 m/s; P<0.05). Dominant frequency analysis in Cx40(-/-) RA demonstrated significant reduction in the area of 1:1 conduction at 16 Hz (40+/-10% versus 69+/-5% in Cx40(+/+)) and 25 Hz (36+/-11% versus 65+/-9% in Cx40(+/+)).
  
  
  CONCLUSIONS
  This is the first demonstration of intra-atrial block, ectopic rhythms, and altered atrial propagation in the RA of Cx40(-/-) mice.
authors.affiliation: Institute for Cardiovascular Research, State University of New York Upstate Medical University, Syracuse, NY 13210, USA.
authors.forename: Suveer
authors.initials: S
authors.lastname: Bagwe
authors.forename: Omer
authors.initials: O
authors.lastname: Berenfeld
authors.forename: Dhananjay
authors.initials: D
authors.lastname: Vaidya
authors.forename: Gregory E
authors.initials: GE
authors.lastname: Morley
authors.forename: José
authors.initials: J
authors.lastname: Jalife
mesh_terms: D000465:Algorithms; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000235:genetics; D002304:Cardiac Pacing, Artificial; D002455:Cell Division; D017630:Connexins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D006325:Heart Atria / Q000166:cytology / Q000503:physiopathology; D006327:Heart Block / Q000235:genetics; D006329:Heart Conduction System / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008959:Models, Neurological; D009431:Neural Conduction / Q000502:physiology; D000097003:Gap Junction alpha-5 Protein
chemical_list: D017630:Connexins; D000097003:Gap Junction alpha-5 Protein