Characterization of Conduction in the Ventricles of Normal and Heterozygous Cx43 Knockout Mice Using Optical Mapping

Abstract

Conduction in Normal and C×43^+/− Mice. 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 C×43‐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 C×43 gene (C×43^−/−) is lethal, the heterozygous (Cx43^+/−) animals survive to adulthood. Reports on the cardiac electrophysiologic phenotype of the C×43^+/− mice are contradictory. Thus, the effects of a null mutation of a single C×43 allele require reevaluation. Methods and Results: High‐resolution video mapping techniques were used to study propagation in hearts from C×43^+/− and littermate control (C×43^+/+) 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 C×43^+/+ and 6 C×43^+/− age matched mice did not show differences in any parameter, including QRS duration (14.5 ± 0.9 and 15.7 ± 2.3 msec for C×43^+/+ and C×43^+/−, 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 C×43^+/− mice, which is consistent with the demonstration that ECG parameter values in the heterozygous mice are the same as those in wild‐type mice.