The gap-junctional protein connexin40 is elevated in patients susceptible to postoperative atrial fibrillation

• Published in: Circulation (New York, N.Y.) Vol. 103; no. 6; pp. 842 - 849
• Main Authors: DUPONT, Emmanuel, KO, Yu-Shien, ROTHERY, Stephen, COPPEN, Steven R, BAGHAI, Max, HAW, Marcus, SEVERS, Nicholas J
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 13-02-2001; American Heart Association, Inc
• Subjects: Aged; Antibodies - immunology; Atrial Fibrillation - blood; Atrial Fibrillation - metabolism; Biological and medical sciences; Blotting, Northern; Blotting, Western; Cardiac dysrhythmias; Cardiology. Vascular system; Connexin 43 - analysis; Connexins - analysis; Connexins - blood; Connexins - immunology; Coronary Artery Bypass; Disease Susceptibility - metabolism; Endothelium, Vascular - metabolism; Female; Fluorescent Antibody Technique; Gap Junction alpha-5 Protein; Heart; Heart Atria; Humans; Immunohistochemistry; Male; Medical sciences; Microscopy, Confocal; Middle Aged; Myocardial Ischemia - surgery; Myocardium - metabolism; Postoperative Complications - blood; Postoperative Complications - metabolism; Retrospective Studies; RNA, Messenger - analysis; Human; Connexin; Arrhythmia; Pathogenesis; Heart disease; Atrial fibrillation; Cardiovascular disease; Excitability disorder; Gap junction
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.cir.103.6.842

Atrial fibrillation (AF), a cardiac arrhythmia arising from atrial re-entrant circuits, is a common complication after cardiac surgery, but the proarrhythmic substrate underlying the development of postoperative AF remains unclear. This study investigated the hypothesis that altered expression of connexins, the component proteins of gap junctions, is a determinant of a predisposition to AF.
The expression of the 3 atrial connexins-connexins 43, 40, and 45-was analyzed at the mRNA and protein levels by Northern and Western blotting techniques and immunoconfocal microscopy in right atrial appendages from patients with ischemic heart disease who were undergoing coronary artery bypass surgery. Twenty percent of the patients subsequently developed AF, which allowed retrospective division of the samples into 2 groups, non-AF and AF. Connexin43 and connexin45 transcript and protein levels did not differ between the groups. However, connexin40 transcript and protein were expressed at significantly higher levels in the AF group. Connexin40 protein was markedly heterogeneous in distribution.
Atrial myocardium susceptible to AF is distinguished from its nonsusceptible counterpart by elevated connexin40 expression. The heterogeneity of connexin distribution could give rise to different resistive properties and conduction velocities in spatially adjacent regions of tissue, which become enhanced and, hence, proarrhythmic the higher the overall level of connexin40.