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Null mutation of connexin43 causes slow propagation of ventricular activation in the late stages of mouse embryonic development.
- Source :
-
Circulation research [Circ Res] 2001 Jun 08; Vol. 88 (11), pp. 1196-202. - Publication Year :
- 2001
-
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<0.005]) and in both ventricles at 17.5 dpc (in RV, WT 8.4 [7.6 to 9.3], Cx43(+/)(-) 8.7 [8.1 to 9.3], and Cx43(-/-) 1.1 [0.1 to 1.3; P<0.005]; in LV, WT 10.1 [9.4 to 10.7], Cx43(+/)(-) 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.
- Subjects :
- Animals
Arrhythmias, Cardiac diagnosis
Arrhythmias, Cardiac embryology
Body Surface Potential Mapping
Cardiac Pacing, Artificial
Connexin 43 genetics
Connexin 43 metabolism
Connexins genetics
Connexins metabolism
Disease Models, Animal
Electrocardiography methods
Electrophysiologic Techniques, Cardiac
Fluorescent Dyes
Heart Conduction System physiopathology
Heart Rate
Heart Ventricles chemistry
Heart Ventricles embryology
Heterozygote
Homozygote
In Vitro Techniques
Mice
Mice, Inbred Strains
Mice, Knockout
Optics and Photonics
RNA, Messenger analysis
RNA, Messenger metabolism
Ventricular Dysfunction embryology
Ventricular Dysfunction genetics
Video Recording
Gap Junction alpha-5 Protein
Arrhythmias, Cardiac physiopathology
Connexin 43 deficiency
Heart Ventricles physiopathology
Ventricular Dysfunction physiopathology
Subjects
Details
- Language :
- English
- ISSN :
- 1524-4571
- Volume :
- 88
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Circulation research
- Publication Type :
- Academic Journal
- Accession number :
- 11397787
- Full Text :
- https://doi.org/10.1161/hh1101.091107