Copyright © 2006, European Society of Cardiology
Chronic hemodynamic overload of the atria is an important factor for gap junction remodeling in human and rat hearts
aCNRS-UMR 8162, Université Paris XI Sud, Hôpital Marie Lannelongue, 133 Avenue de la Résistance, 92350 Le Plessis Robinson, France
bCardiovascular Research Center Inserm Lariboisiere, Paris, France
cINSERM U570, Université Paris 5, France
dInstitut-Jacques-Monod-UMR7592 CNRS-Universités Paris 6/Paris 7, France
eINSERM U460, Paris, France
fINSERM, UMRS621; Université Pierre et Marie Curie-Paris6, Paris, France
* Corresponding author. Tel.: +33 1 40 94 25 20; fax: +33 1 40 94 25 22. Email address: catherine.rucker{at}ccml.u-psud.fr
Objectives: 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.
Conclusion: 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.
KEYWORDS Connexins; Gap junction; Atrial myocardium; Fibrosis; Atrial fibrillation
1 Current address: CNRS-UMR 5471, Talence, France.
2 Current address: Laboratoire de Chimie Physique, Université Paris-XI, Orsay, France.
Time for primary review 23 days
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