From the Departments of Medicine, Surgery, Pediatrics, and Pathology,
Washington University, St Louis, Mo (S.A.T., R.B.S., M.A.B., E.C.B., J.E.S.),
and Molecular Cardiology Research Center, New England Medical Center, Boston,
Mass (C.I.B., M.E.M.).
Correspondence to Jeffrey E. Saffitz, MD, PhD, Department of Pathology, Box 8118, Washington University School of Medicine, 660 S Euclid Ave, St Louis, MO 63110. E-mail saffitz{at}pathology.wustl.edu
Background—Myocardial conduction
depends on intercellular transfer of currrent at gap junctions. Atrial
myocytes express three different gap junction channel
proteins—connexin43 (Cx43), connexin45 (Cx45), and connexin40
(Cx40)—whereas ventricular myocytes express only Cx43 and
Cx45. However, the physiological roles of
individual connexins are unknown. We have previously shown that mice
heterozygous for a null mutation in the gene encoding Cx43
(Cx43+/- mice) express 50% of the normal amount of Cx43
in ventricular myocardium and exhibit marked
slowing of ventricular conduction.
Methods and Results—To determine whether atrial conduction is
affected in Cx43+/- mice, we measured atrial conduction
velocity in isolated hearts, performed detailed ECG and
electrophysiological studies in intact
animals, and determined the amount of cardiac connexins in atrial and
ventricular tissue. Ventricular conduction
velocity was reduced by 38% in Cx43+/- mice compared with
wild-types, but atrial conduction velocity in the same hearts was
normal. QRS duration was significantly greater in Cx43+/-
mice than in wild-types, but P-wave duration and amplitude did not
differ. Atrial expression of Cx43 was reduced by 50%.
Conclusions—These results indicate that Cx43 is a principal
conductor of intercellular current in the ventricle because
ventricular conduction is significantly slowed when Cx43
content is reduced by only 50%. In contrast, a similar reduction in
Cx43 content in atrial muscle has no effect on atrial conduction,
suggesting that Cx40 (which is expressed in atrial but not
ventricular myocytes) is a major electrical coupling
protein in atrial muscle. Thus, Cx43 and Cx40 may be chamber-specific
determinants of myocardial conduction.
© 1998 American Heart Association, Inc.
Basic Science Reports
Disparate Effects of Deficient Expression of Connexin43 on Atrial and Ventricular Conduction
Evidence for Chamber-Specific Molecular Determinants of Conduction
Key Words: connexin • conduction • tachyarrhythmias • proteins
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