title: High resolution optical mapping reveals conduction slowing in connexin43 deficient mice.
abstract: 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.
authors.affiliation: The Heart and Vascular Research Center, MetroHealth Campus, Case Western Reserve University, 2500 MetroHealth Drive, Hamman 322, Cleveland, OH 44109-1998, USA.
authors.forename: B C
authors.initials: BC
authors.lastname: Eloff
authors.forename: D L
authors.initials: DL
authors.lastname: Lerner
authors.forename: K A
authors.initials: KA
authors.lastname: Yamada
authors.forename: R B
authors.initials: RB
authors.lastname: Schuessler
authors.forename: J E
authors.initials: JE
authors.lastname: Saffitz
authors.forename: D S
authors.initials: DS
authors.lastname: Rosenbaum
mesh_terms: 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
chemical_list: D018031:Connexin 43