Null Mutation of Connexin43 Causes Slow Propagation of Ventricular Activation in the Late Stages of Mouse Embryonic Development
Open Access
- 8 June 2001
- journal article
- other
- Published by Ovid Technologies (Wolters Kluwer Health) in Circulation Research
- Vol. 88 (11), 1196-1202
- https://doi.org/10.1161/hh1101.091107
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<0.005]) corresponding with the downregulation of Cx40. Cx40 and Cx45 mRNAs were detectable in ventricular homogenates even at 17.5 dpc, probably accounting for the residual conduction function. Neonatal knockout hearts were arrhythmic in vivo as well as ex vivo. This study demonstrates the contribution of Cx43 to the electrical function of the developing mouse heart and the essential role of this gene in maintaining heart rhythm in postnatal life.Keywords
This publication has 28 references indexed in Scilit:
- Voltage-Gated Na+Channel Activity and Connexin Expression in C×43-Deficient Cardiac MyocytesJournal of Cardiovascular Electrophysiology, 1999
- Connexin45 (?6) expression delineates an extended conduction system in the embryonic and mature rodent heartDevelopmental Genetics, 1999
- Structure of Cardiac Gap Junction Intercellular ChannelsJournal of Structural Biology, 1998
- Hypoxia and Hypothermia Enhance Spatial Heterogeneities of Repolarization in Guinea Pig Hearts:.Journal of Cardiovascular Electrophysiology, 1998
- Slow ventricular conduction in mice heterozygous for a connexin43 null mutation.JCI Insight, 1997
- Gap Junction Protein Phenotypes of the Human Heart and Conduction SystemJournal of Cardiovascular Electrophysiology, 1995
- Distinct gap junction protein phenotypes in cardiac tissues with disparate conduction propertiesJournal of the American College of Cardiology, 1994
- Stationary and drifting spiral waves of excitation in isolated cardiac muscleNature, 1992
- Changes in the expression of connexin 43, a cardiac gap junctional protein, during mouse heart developmentJournal of Molecular and Cellular Cardiology, 1990
- Maturation of Responsiveness to Cardioactive DrugsJCI Insight, 1973