title: Calcium dysregulation in atrial fibrillation: the role of CaMKII.
abstract: Atrial fibrillation (AF) is the most frequently encountered clinical arrhythmia and is associated with increased morbidity and mortality. Ectopic activity and reentry are considered major arrhythmogenic mechanisms contributing to the initiation and maintenance of AF. In addition, AF is self-reinforcing through progressive electrical and structural remodeling which stabilize the arrhythmia and make it more difficult to treat. Recent research has suggested an important role for Ca(2+)-dysregulation in AF. Ca(2+)-handling abnormalities may promote ectopic activity, conduction abnormalities facilitating reentry, and AF-related remodeling. In this review article, we summarize the Ca(2+)-handling derangements occurring in AF and discuss their impact on fundamental arrhythmogenic mechanisms. We focus in particular on the role of the multifunctional Ca(2+)/calmodulin-dependent protein kinase type-II (CaMKII), which acts as a major link between Ca(2+)-dysregulation and arrhythmogenesis. CaMKII expression and activity are increased in AF and promote arrhythmogenesis through phosphorylation of various targets involved in cardiac electrophysiology and excitation-contraction coupling. We discuss the implications for potential novel therapeutic strategies for AF based on CaMKII and Ca(2+)-handling abnormalities.
authors.affiliation: Institute of Pharmacology, Faculty of Medicine, University Duisburg-Essen Essen, Germany.
authors.forename: Jordi
authors.initials: J
authors.lastname: Heijman
authors.affiliation: Institute of Pharmacology, Faculty of Medicine, University Duisburg-Essen Essen, Germany.
authors.forename: Niels
authors.initials: N
authors.lastname: Voigt
authors.affiliation: Cardiovascular Research Institute, Departments of Molecular Physiology and Biophysics, and Medicine-Cardiology, Baylor College of Medicine Houston, TX, USA.
authors.forename: Xander H T
authors.initials: XH
authors.lastname: Wehrens
authors.affiliation: Institute of Pharmacology, Faculty of Medicine, University Duisburg-Essen Essen, Germany.
authors.forename: Dobromir
authors.initials: D
authors.lastname: Dobrev
keywords: CaMKII; atrial fibrillation; calcium; ectopic activity; reentry