High resolution optical mapping reveals conduction slowing in connexin43 deficient mice.
Analysis of mice with genetically altered expression of cardiac connexins can provide insights into the role of individual gap junction channel proteins in cell-to-cell communication, impulse propagation, and arrhythmias. However, conflicting results have been reported regarding conduction velocity slowing in mice heterozygous for a null mutation in the gene encoding connexin43 (Cx43).


METHODS
High-resolution optical mapping was used to record action potentials from 256 sites, simultaneously, on the ventricular surface of Langendorff perfused hearts from 15 heterozygous (Cx43+/-) and 8 wildtype (Cx43+/+) mice (controls). A sensitive method for measuring epicardial conduction velocity was developed to minimize confounding influences of subepicardial breakthrough and virtual electrode effects.


RESULTS
Epicardial conduction velocity was significantly slower (23 to 35%, P<0.01) in Cx43+/- mice compared to wildtype. There was no change in conduction patterns or anisotropic ratio (Cx43+/- 1.54+/-0.33; Cx43+/+ 1.57+/-0.17) suggesting that Cx43 expression was reduced uniformly throughout myocardium. The magnitude of reductions in conduction velocity and Cx43 protein expression (45%) were similar in mice in which the null allele occurred in a pure C57BL/6J genetic background versus a mixed (C57BL/6J X 129) background. Action potential duration did not differ between mice of different genotypes.


CONCLUSIONS
A approximately 50% reduction of Cx43 expression causes significant conduction velocity slowing in the Cx43+/- mouse heart. The apparent lack of conduction velocity changes reported in previous studies may be related to technical factors rather than variations in genetic background. High-resolution optical mapping is a powerful tool for investigating molecular determinants of propagation and arrhythmias in genetically engineered mice.
Eloff
B C
BC
The Heart and Vascular Research Center, MetroHealth Campus, Case Western Reserve University, 2500 MetroHealth Drive, Hamman 322, Cleveland, OH 44109-1998, USA.
Lerner
D L
DL
Yamada
K A
KA
Schuessler
R B
RB
Saffitz
J E
JE
Rosenbaum
D S
DS
D000200:Action Potentials; D000704:Analysis of Variance; D000818:Animals; D018031:Connexin 43 / Q000235:genetics* / Q000378:metabolism; D015151:Immunoblotting; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008856:Microscopy, Fluorescence; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism*; D010477:Perfusion; D011690:Purkinje Fibers / Q000473:pathology; D014741:Video Recording
D018031:Connexin 43