Alterations of atrial Ca(2+) handling as cause and consequence of atrial fibrillation.

Atrial fibrillation (AF) is the most prevalent sustained arrhythmia. As the most important risk factor for embolic stroke, AF is associated with a high morbidity and mortality. Despite decades of research, successful (pharmacological and interventional) 'ablation' of the arrhythmia remains challenging. AF is characterized by a diverse aetiology, including heart failure, hypertension, and valvular disease. Based on this understanding, new treatment strategies that are specifically tailored to the underlying pathophysiology of a certain 'type' of AF are being developed. One important aspect of AF pathophysiology is altered intracellular Ca(2+) handling. Due to the increase in the atrial activation rate and the subsequent initial [Ca(2+)](i) overload, AF induces 'remodelling' of intracellular Ca(2+) handling. Current research focuses on unravelling the contribution of altered intracellular Ca(2+) handling to different types of AF. More specifically, changes in intracellular Ca(2+) homeostasis preceding the onset of AF, in conditions which predispose to AF (e.g. heart failure), appear to be different from changes in Ca(2+) handling developing after the onset of AF. Here we review and critique altered intracellular Ca(2+) handling and its contribution to three specific aspects of AF pathophysiology, (i) excitation-transcription coupling and Ca(2+)-dependent signalling pathways, (ii) atrial contractile dysfunction, and (iii) arrhythmogenicity.