title: The gap-junctional protein connexin40 is elevated in patients susceptible to postoperative atrial fibrillation.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: National Heart and Lung Institute, Imperial College, London, UK. Dr Ko is currently affiliated with Chang-Gung Memorial Hospital, Taipei, Taiwan.
authors.forename: E
authors.initials: E
authors.lastname: Dupont
authors.forename: Y
authors.initials: Y
authors.lastname: Ko
authors.forename: S
authors.initials: S
authors.lastname: Rothery
authors.forename: S R
authors.initials: SR
authors.lastname: Coppen
authors.forename: M
authors.initials: M
authors.lastname: Baghai
authors.forename: M
authors.initials: M
authors.lastname: Haw
authors.forename: N J
authors.initials: NJ
authors.lastname: Severs
mesh_terms: D000368:Aged; D000906:Antibodies / Q000276:immunology; D001281:Atrial Fibrillation / Q000097:blood / Q000378:metabolism*; D015152:Blotting, Northern; D015153:Blotting, Western; D018031:Connexin 43 / Q000032:analysis; D017630:Connexins / Q000032:analysis* / Q000097:blood / Q000276:immunology; D001026:Coronary Artery Bypass; D004198:Disease Susceptibility / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D006325:Heart Atria; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000601:surgery; D009206:Myocardium / Q000378:metabolism*; D011183:Postoperative Complications / Q000097:blood / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D012189:Retrospective Studies; D000097003:Gap Junction alpha-5 Protein
chemical_list: D000906:Antibodies; D018031:Connexin 43; D017630:Connexins; D012333:RNA, Messenger; D000097003:Gap Junction alpha-5 Protein; C082920:connexin 45