High resolution optical mapping reveals conduction slowing in connexin43 deficient mice

Benjamin C. Eloff, Deborah L. Lerner, Kathryn A. Yamada, Richard B. Schuessler, Jeffrey E. Saffitz, David S. Rosenbaum

Research output: Contribution to journalArticle

125 Scopus citations

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 ∼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.

Original languageEnglish
Pages (from-to)681-690
Number of pages10
JournalCardiovascular Research
Volume51
Issue number4
DOIs
StatePublished - Sep 11 2001

Keywords

  • Cell communication
  • Gap junctions
  • Gene expression
  • Mapping

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