© 2000 American Heart Association, Inc.
Integrative Physiology |
High-Resolution Optical Mapping of the Right Bundle Branch in Connexin40 Knockout Mice Reveals Slow Conduction in the Specialized Conduction System
From the Department of Pharmacology (H.S.T., D.V., J.J., G.E.M.), SUNY Upstate Medical University, Syracuse, NY; the Department of Physiology (A.M.S.), University of Arizona, Tucson, Ariz; and the Department of Neurobiology (D.L.P.), Harvard Medical School, Boston, Mass.
Correspondence to Gregory E. Morley, PhD, Department of Pharmacology, SUNY Upstate Medical University, 766 Irving Ave, Syracuse, NY 13210. E-mail morleyg{at}mail.upstate.edu
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 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.
Key Words: optical mapping • specialized conduction system • knockout mice • connexin40
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