Altered right atrial excitation and propagation in connexin40 knockout mice.
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.
Bagwe
Suveer
S
Institute for Cardiovascular Research, State University of New York Upstate Medical University, Syracuse, NY 13210, USA.
Berenfeld
Omer
O
Vaidya
Dhananjay
D
Morley
Gregory E
GE
Jalife
José
J
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
D017630:Connexins; D000097003:Gap Junction alpha-5 Protein