Null Mutation of Connexin43 Causes Slow Propagation of Ventricular Activation in the Late Stages of Mouse Embryonic Development

Abstract —Connexin43 (Cx43) is the principal connexin isoform in the mouse ventricle, where it is thought to provide electrical coupling between cells. Knocking out this gene results in anatomic malformations that nevertheless allow for survival through early neonatal life. We examined electrical wave propagation in the left (LV) and right (RV) ventricles of isolated Cx43 null mutated (Cx43 −/− ), heterozygous (Cx43 +/ − ), and wild-type (WT) embryos using high-resolution mapping of voltage-sensitive dye fluorescence. Consistent with the compensating presence of the other connexins, no reduction in propagation velocity was seen in Cx43 −/− ventricles at postcoital day (dpc) 12.5 compared with WT or Cx43 +/ − ventricles. A gross reduction in conduction velocity was seen in the RV at 15.5 dpc (in cm/second, mean [1 SE confidence interval], WT 9.9 [8.7 to 11.2], Cx43 +/ − 9.9 [9.0 to 10.9], and Cx43 −/− 2.2 [1.8 to 2.7; P +/ − 8.7 [8.1 to 9.3], and Cx43 −/− 1.1 [0.1 to 1.3; P +/ − 8.3 [7.8 to 8.9], and Cx43 −/− 1.7 [1.3 to 2.1; P