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-cel l communication and conduction of electrical impulses. Video maps of the ve ntricular epicardium and the proximal segment of the right bundle branch (R BB) were obtained using a high-speed CCD camera while simultaneously record ing 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 bre akthroughs that originated first on the right ventricle (RV) and then the l eft ventricle (LV), In Cx40(-/-) hearts, the RV breakthrough occurred after the LV breakthrough. Additionally, Cx40(-/-) mice showed RV breakthrough t imes 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 fro m 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 a ddition, simultaneous ECG records demonstrated significant delays n Cx40(-/ -) RBB activation time with respect to P time (P-RBB rime; 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 fir st direct demonstration of conduction defects in the specialized conduction system of Cx40(-/-) mice and provide new insight into the role of gap junc tions in cardiac impulse propagation.