Cardiac connexins as candidate genes for idiopathic atrial fibrillation.
OBJECTIVE
Atrial fibrillation is the most common sustained cardiac arrhythmia and may cause significant morbidity. Current management strategies offer only modest success and may be associated with intolerable drug side effects or risk of procedural complications. As with other cardiac arrhythmias, the identification of genetic determinants predisposing to atrial fibrillation may provide novel molecular targets for drug development. This review discusses the role of cardiac connexins in the heart and suggests that genetic defects in cardiac connexins may predispose to arrhythmia vulnerability.


RESULTS
Animal models deficient in cardiac connexins demonstrate abnormalities in myocardial tissue conduction and vulnerability to re-entrant arrhythmias, including ventricular tachycardia and atrial fibrillation. Atrial tissue analyses from human patients with atrial fibrillation consistently demonstrate alterations in connexin distribution and protein levels, suggesting a role of connexins in the perpetuation of the arrhythmia. Most recently, genetic studies of Cx43 and Cx40 indicate that genetic variations in these genes may predispose to arrhythmia vulnerability in humans.


CONCLUSIONS
Current data support the critical role of cardiac connexins in mediating coordinated electrical activation and conduction through myocardial tissue. Alterations in the tissue distribution or function of cardiac connexins may predispose to cardiac arrhythmias, supporting a previously proposed hypothesis that cardiac connexins should be considered a major therapeutic target in the management of atrial fibrillation.
Gollob
Michael H
MH
University of Ottawa Heart Institute, Ottawa, Ontario, Canada. MGollob@ottawaheart.ca
D000818:Animals; D001281:Atrial Fibrillation / Q000235:genetics*; D018031:Connexin 43 / Q000235:genetics / Q000502:physiology; D017630:Connexins / Q000235:genetics* / Q000502:physiology; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D017629:Gap Junctions / Q000502:physiology; D006801:Humans; D051379:Mice; D018345:Mice, Knockout
D018031:Connexin 43; D017630:Connexins