Atrial Ca2+ signaling in atrial fibrillation as an antiarrhythmic drug target

Atrial fibrillation (AF) is the most frequent arrhythmia and is associated with increased morbidity and mortality. Current drugs for AF treatment have moderate efficacy and increase the risk of life-threatening antiarrhythmias, making novel drug development crucial. Newer antiarrhythmic drugs like dronedarone and possibly vernakalant are efficient and may have less proarrhythmic potential. Emerging evidence suggests that abnormal intracellular Ca(2+) signaling is the key contributor to focal firing, substrate evolution, and atrial remodeling during AF. Accordingly, identification of the underlying atrial Ca(2+)-handling abnormalities is expected to discover novel mechanistically based therapeutic targets. This article reviews the molecular mechanisms of altered Ca(2+) signaling in AF and discusses the potential value of novel approaches targeting atrial Ca(2+)-handling abnormalities.