High-resolution optical mapping of the right bundle branch in connexin40 knockout mice reveals slow conduction in the specialized conduction system

Circ Res. 2000 Nov 10;87(10):929-36. doi: 10.1161/01.res.87.10.929.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylthiocholine
  • Animals
  • Bundle of His / metabolism
  • Cardiac Pacing, Artificial
  • Connexins / deficiency
  • Connexins / genetics
  • Connexins / metabolism*
  • Electrocardiography / methods
  • Gap Junctions / metabolism
  • Heart Conduction System / physiology*
  • Heart Rate / genetics
  • Heart Ventricles / metabolism
  • In Vitro Techniques
  • Mice
  • Mice, Knockout
  • Myocardium / metabolism
  • Purkinje Fibers / metabolism


  • Connexins
  • connexin 40
  • Acetylthiocholine