High-resolution optical mapping of the right bundle branch in connexin40 knockout mice reveals slow conduction in the specialized conduction system.
Connexin40 (Cx40) is a major gap junction protein that is expressed in the His-Purkinje system and thought to be a critical determinant of cell-to-cell communication and conduction of electrical impulses. Video maps of the ventricular epicardium and the proximal segment of the right bundle branch (RBB) were obtained using a high-speed CCD camera while simultaneously recording volume-conducted ECGs. In Cx40(-/-) mice, the PR interval was prolonged (47.4+/-1.4 in wild-type [WT] [n=6] and 57.5+/-2.8 in Cx40(-/-) [n=6]; P<0.01). WT ventricular epicardial activation was characterized by focused breakthroughs that originated first on the right ventricle (RV) and then the left ventricle (LV). In Cx40(-/-) hearts, the RV breakthrough occurred after the LV breakthrough. Additionally, Cx40(-/-) mice showed RV breakthrough times that were significantly delayed with respect to QRS complex onset (3.7+/-0.7 ms in WT [n=6] and 6.5+/-0.7 ms in Cx40(-/-) [n=6]; P<0.01), whereas LV breakthrough times did not change. Conduction velocity measurements from optical mapping of the RBB revealed slow conduction in Cx40(-/-) mice (74.5+/-3 cm/s in WT [n=7] and 43.7+/-6 cm/s in Cx40(-/-) [n=7]; P<0.01). In addition, simultaneous ECG records demonstrated significant delays in Cx40(-/-) RBB activation time with respect to P time (P-RBB time; 41.6+/-1.9 ms in WT [n=7] and 55.1+/-1.3 ms in [n=7]; P<0.01). These data represent the first direct demonstration of conduction defects in the specialized conduction system of Cx40(-/-) mice and provide new insight into the role of gap junctions in cardiac impulse propagation.
Tamaddon
H S
HS
Department of Pharmacology, SUNY Upstate Medical University, Syracuse, NY, USA.
Vaidya
D
D
Simon
A M
AM
Paul
D L
DL
Jalife
J
J
Morley
G E
GE
D000122:Acetylthiocholine; D000818:Animals; D002036:Bundle of His / Q000378:metabolism; D002304:Cardiac Pacing, Artificial; D017630:Connexins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D004562:Electrocardiography / Q000379:methods; D017629:Gap Junctions / Q000378:metabolism; D006329:Heart Conduction System / Q000502:physiology*; D006339:Heart Rate / Q000235:genetics; D006352:Heart Ventricles / Q000378:metabolism; D066298:In Vitro Techniques; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism; D011690:Purkinje Fibers / Q000378:metabolism; D000097003:Gap Junction alpha-5 Protein
D000122:Acetylthiocholine; D017630:Connexins; D000097003:Gap Junction alpha-5 Protein