Conduction slowing and sudden arrhythmic death in mice with cardiac-restricted inactivation of connexin43. Academic Article uri icon

Overview

MeSH

  • Animals
  • Blotting, Western
  • Echocardiography
  • Female
  • Fetal Heart
  • Fluorescent Antibody Technique
  • Genotype
  • Heart Ventricles
  • Male
  • Mice
  • Mice, Knockout
  • Myocardium
  • Survival Analysis
  • Survival Rate

MeSH Major

  • Arrhythmias, Cardiac
  • Connexin 43
  • Death, Sudden, Cardiac
  • Heart Conduction System

abstract

  • Cardiac arrhythmia is a common and often lethal manifestation of many forms of heart disease. Gap junction remodeling has been postulated to contribute to the increased propensity for arrhythmogenesis in diseased myocardium, although a causative role in vivo remains speculative. By generating mice with cardiac-restricted knockout of connexin43 (Cx43), we have circumvented the perinatal lethal developmental defect associated with germline inactivation of this gap junction channel gene and uncovered an essential role for Cx43 in the maintenance of electrical stability. Mice with cardiac-specific loss of Cx43 have normal heart structure and contractile function, and yet they uniformly (28 of 28 conditional Cx43 knockout mice observed) develop sudden cardiac death from spontaneous ventricular arrhythmias by 2 months of age. Optical mapping of the epicardial electrical activation pattern in Cx43 conditional knockout mice revealed that ventricular conduction velocity was significantly slowed by up to 55% in the transverse direction and 42% in the longitudinal direction, resulting in an increase in anisotropic ratio compared with control littermates (2.1+/-0.13 versus 1.66+/-0.06; P:<0.01). This novel genetic murine model of primary sudden cardiac death defines gap junctional abnormalities as a key molecular feature of the arrhythmogenic substrate.

publication date

  • February 16, 2001

has subject area

  • Animals
  • Arrhythmias, Cardiac
  • Blotting, Western
  • Connexin 43
  • Death, Sudden, Cardiac
  • Echocardiography
  • Female
  • Fetal Heart
  • Fluorescent Antibody Technique
  • Genotype
  • Heart Conduction System
  • Heart Ventricles
  • Male
  • Mice
  • Mice, Knockout
  • Myocardium
  • Survival Analysis
  • Survival Rate

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3630465

PubMed ID

  • 11179202

Additional Document Info

start page

  • 333

end page

  • 339

volume

  • 88

number

  • 3