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

Abstract

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.