Cardiac connexins as candidate genes for idiopathic atrial fibrillation.

Abstract

PURPOSE OF REVIEW:

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.

RECENT FINDINGS:

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.

SUMMARY:

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.

• Authors: Michael H Gollob
• Journal: Current opinion in cardiology (Curr Opin Cardiol) Vol. 21 Issue 3 Pg. 155-8 (May 2006) ISSN: 0268-4705 [Print] United States
• PMID: 16601450 (Publication Type: Journal Article, Review)

Chemical References

• Connexin 43
• Connexins

Topics

• Animals
• Atrial Fibrillation (genetics)
• Connexin 43 (genetics, physiology)
• Connexins (genetics, physiology)
• Disease Models, Animal
• Disease Susceptibility
• Gap Junctions (physiology)
• Humans
• Mice
• Mice, Knockout