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

Houman S. Tamaddon, Dhananjay Vaidya, Alexander M. Simon, David L. Paul, José Jalife, Gregory E. Morley

Research output: Contribution to journalArticle

134 Scopus citations

Abstract

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 fight 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 fight 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.

Original languageEnglish (US)
Pages (from-to)929-936
Number of pages8
JournalCirculation research
Volume87
Issue number10
DOIs
StatePublished - Nov 10 2000

Keywords

  • Connexin40
  • Knockout mice
  • Optical mapping
  • Specialized conduction system

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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