Computational and experimental models of Ca2+-dependent arrhythmias

Compelling evidence exists that in cardiac muscle cells, defects in release of calcium (Ca2+) from intracellular stores are responsible for triggering and/or maintenance of arrhythmias in at least some disorders. To better understand Ca2+-triggered arrhythmias in patients, the past several years have seen the development of in vitro pharmacological models using heart cells from animals, and, more recently, in vivo models of genetically modified mice. Here, we review several models that have been used to understand these arrhythmias, pointing out strengths and weaknesses of different approaches. We further argue that, because of the complexity of cardiac electrical and Ca2+ signaling, in silico computational models are likely to become increasingly important to understand quantitatively the competing effects that control potentially arrhythmogenic Ca2+ release in the heart.

Section editors:Colleen E. Clancy – Department of Pharmacology, University of California, Davis, CA 95616-8636, USAFadi G. Akar – Cardiovascular Institute, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA