Effects of chronic atrial fibrillation on gap junction distribution in human and rat atria

• Published in: Journal of the American College of Cardiology Vol. 38; no. 3; pp. 883 - 891
• Main Authors: Polontchouk, Lioudmila, Haefliger, Jacques-Antoine, Ebelt, Berit, Schaefer, Thomas, Stuhlmann, Dominik, Mehlhorn, Uwe, Kuhn-Regnier, Ferdinand, De Vivie, E.Rainer, Dhein, Stefan
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-09-2001; Elsevier Science
• Subjects: Aged; Animals; Anisotropy; Atrial Fibrillation - metabolism; Biological and medical sciences; Blotting, Western; Cardiac dysrhythmias; Cardiology. Vascular system; Chronic Disease; Connexin 43 - metabolism; Connexins - metabolism; Electrophysiologic Techniques, Cardiac; Gap Junction alpha-5 Protein; Gap Junctions - metabolism; Heart; Heart Atria - metabolism; Humans; Immunohistochemistry; In Vitro Techniques; Medical sciences; Middle Aged; Models, Animal; Rats; Tissue Distribution; Cx40; SDS-PAGE; Cx43; AF; Vl; anisotropy; d.U; Vt; ECL; SR; Human; Immunohistochemistry; Arrhythmia; Rat; Atrial fibrillation; Rodentia; Electrophysiology; Cardiovascular disease; Excitability disorder; Gap junction; Pathology; Vertebrata; Chronic; Mammalia; Heart disease; Animal; Right atrium
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/S0735-1097(01)01443-7

OBJECTIVES
To elucidate the structural basis for the electrophysiologic remodeling induced by chronic atrial fibrillation (AF), we investigated connexin40 and connexin43 (Cx40 and Cx43) expression and distribution in atria of patients with and without chronic AF and in an animal model of AF with additional electrophysiologic investigation of anisotropy (ratio of longitudinal and transverse velocities).
BACKGROUND
Atrial fibrillation is a common arrhythmia that has a tendency to become persistent. Since gap junctions provide the syncytial properties of the atrium, changes in expression and distribution of intercellular connections may accompany the chronification of AF.
METHODS
Atrial tissues isolated from 12 patients in normal sinus rhythm at the time of cardiac surgery and from 12 patients with chronic AF were processed for immunohistology and immunoblotting for the detection of the gap junction proteins. The functional study of the cardiac tissue anisotropy was performed in rat atria in which AF was induced by 24 h of rapid pacing (10 Hz).
RESULTS
Immunoblotting revealed that AF did not induce any significant change in Cx43 content in human atria. In contrast, a 2.7-fold increase in expression of Cx40 was observed in AF. Immunohistologic analysis indicated that AF resulted in an increase in the immunostaining of both connexins at the lateral membrane of human atrial cells. A similar spatial redistribution of the Cx43 signal was seen in isolated rat atria with experimentally-induced AF. In addition, AF in rat atria resulted in decreased anisotropy with slightly enhanced transverse conduction velocity.
CONCLUSIONS
This experimental study showed that AF is accompanied by spatial remodeling of gap junctions that might induce changes in the biophysical properties of the tissue.