Characterization of conduction in the ventricles of normal and heterozygous Cx43 knockout mice using optical mapping

Abstract

Introduction: Gap junction channels are important determinants of conduction in the heart and may play a central role in the development of lethal cardiac arrhythmias. The recent development of a Cx43-deficient mouse has raised fundamental questions about the role of specific connexin isoforms in intercellular communication in the heart. Although a homozygous null mutation of the Cx43 gene (Cx43-/-) is lethal, the heterozygous (Cx43+/-) animals survive to adulthood. Reports on the cardiac electrophysiologic phenotype of the Cx43+/- mice are contradictory. Thus, the effects of a null mutation of a single Cx43 allele require reevaluation.

Methods and results: High-resolution video mapping techniques were used to study propagation in hearts from Cx43+/- and littermate control (Cx43+/+) mice. Local conduction velocities (CVs) and conduction patterns were quantitatively measured by determining conduction vectors. We undertook the characterization of ECG parameters and epicardial CVs of normal and Cx43+/- mouse hearts. ECG measurements obtained from 12 Cx43+/+ and 6 Cx43+/- age matched mice did not show differences in any parameter, including QRS duration (14.5 +/- 0.9 and 15.7 +/- 2.3 msec for Cx43+/+ and Cx43+/-, respectively). In addition, using a sensitive method of detecting changes in local CV, video images of epicardial wave propagation revealed similar activation patterns and velocities in both groups of mice.

Conclusion: A sensitive method that accurately measures local CVs throughout the ventricles revealed no changes in Cx43+/- mice, which is consistent with the demonstration that ECG parameter values in the heterozygous mice are the same as those in wild-type mice.