title: Chronic hemodynamic overload of the atria is an important factor for gap junction remodeling in human and rat hearts.
abstract: OBJECTIVE
  The expression and distribution of connexins is abnormal in a number of cardiac diseases, including atrial fibrillation, and is believed to favor conduction slowing and arrhythmia. Here, we studied the role of atrial structural remodeling in the disorganization of gap junctions and whether redistributed connexins can form new functional junction channels.
  
  
  METHODS
  Expression of connexin-43 (Cx43) was characterized by immunoblotting and immunohistochemistry in human right atrial specimens and in rat atria after myocardial infarction (MI). Gap junctions were studied by electron and 3-D microscopy, and myocyte-myocyte coupling was determined by Lucifer yellow dye transfer.
  
  
  RESULTS
  In both chronically hemodynamically overloaded human atria in sinus rhythm and in dilated atria from MI-rats, Cx43 were dephosphorylated and redistributed from the intercalated disc to the lateral cell membranes as observed during atrial fibrillation. In MI-rats, the gap junctions at the intercalated disc were smaller (20% decrease) and contained very little Cx43 (0 or 1 gold particle vs. 42 to 98 in sham-operated rats). In the lateral membranes of myocytes, numerous connexon aggregates comprising non-phosphorylated Cx43 were observed. These connexon aggregates were in no case assembled into gap junction plaque-like structures. However, N-cadherin was well organized in the intercalated disc. There was very little myocyte-myocyte coupling in MI-rat atria and no myocyte-fibroblast coupling. Regression of the atrial remodeling was associated with the normalization of Cx43 localization.
  
  
  CONCLUSIONS
  Structural alteration of the atrial myocardium is an important factor in the disorganization of connexins and gap junction. Moreover, redistributed Cx43 do not form junction channels.
authors.affiliation: CNRS-UMR 8162, Université Paris XI Sud, Hôpital Marie Lannelongue, 133 Avenue de la Résistance, 92350 Le Plessis Robinson, France. catherine.rucker@ccml.u-psud.fr
authors.forename: Catherine
authors.initials: C
authors.lastname: Rucker-Martin
authors.forename: Paul
authors.initials: P
authors.lastname: Milliez
authors.forename: Sisareuth
authors.initials: S
authors.lastname: Tan
authors.forename: Xavier
authors.initials: X
authors.lastname: Decrouy
authors.forename: Michel
authors.initials: M
authors.lastname: Recouvreur
authors.forename: Roger
authors.initials: R
authors.lastname: Vranckx
authors.forename: Claude
authors.initials: C
authors.lastname: Delcayre
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Renaud
authors.forename: Irene
authors.initials: I
authors.lastname: Dunia
authors.forename: Dominique
authors.initials: D
authors.lastname: Segretain
authors.forename: Stéphane N
authors.initials: SN
authors.lastname: Hatem
mesh_terms: D000818:Animals; D001281:Atrial Fibrillation / Q000378:metabolism / Q000473:pathology*; D002450:Cell Communication; D018031:Connexin 43 / Q000032:analysis*; D005355:Fibrosis; D005614:Freeze Fracturing; D017629:Gap Junctions / Q000378:metabolism / Q000473:pathology*; D006325:Heart Atria / Q000378:metabolism / Q000648:ultrastructure*; D006801:Humans; D021621:Imaging, Three-Dimensional; D015151:Immunoblotting; D007150:Immunohistochemistry; D008854:Microscopy, Electron; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology; D051381:Rats
chemical_list: D018031:Connexin 43