Alterations of atrial Ca2+ 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 Ca2+ handling. Due to the increase in the atrial activation rate and the subsequent initial [Ca2+]i overload, AF induces 'remodelling' of intracellular Ca2+ handling. Current research focuses on unravelling the contribution of altered intracellular Ca2+ handling to different types of AF. More specifically, changes in intracellular Ca2+ homeostasis preceding the onset of AF, in conditions which predispose to AF (e.g. heart failure), appear to be different from changes in Ca2+ handling developing after the onset of AF. Here we review and critique altered intracellular Ca2+ 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. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2010.