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

Background-Atrial fibrillation (AF), a cardiac arrhythmia arising from atri al 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 expre ssion of connexins, the component proteins of gap junctions, is a determina nt of a predisposition to AF. Methods and Results-The expression of the 3 atrial connexins-connexins 43, 40, and 45-was analyzed at the mRNA and protein levels by Northern and West ern blotting techniques and immunoconfocal microscopy in right atrial appen dages from patients with ischemic heart disease who were undergoing coronar y artery bypass surgery. Twenty percent of the patients subsequently develo ped 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 w ere expressed at significantly higher levels in the AF group. Connexin40 pr otein was markedly heterogeneous in distribution. Conclusions-Atrial myocardium susceptible to AF is distinguished from its n onsusceptible counterpart by elevated connexin40 expression. The heterogene ity of connexin distribution could give rise to different resistive propert ies and conduction velocities in spatially adjacent regions of tissue, whic h became enhanced and, hence, proarrhythmic the higher the overall level of connexin40.