The virtual sinoatrial node: What did computational models tell us about cardiac pacemaking?

Since its discovery, the sinoatrial node (SAN) has represented a fascinating and complex matter of research. Despite over a century of discoveries, a full comprehension of pacemaking has still to be achieved. Experiments often produced conflicting evidence that was used either in support or against alternative theories, originating intense debates. In this context, mathematical descriptions of the phenomena underlying the heartbeat have grown in importance in the last decades since they helped in gaining insights where experimental evaluation could not reach. This review presents the most updated SAN computational models and discusses their contribution to our understanding of cardiac pacemaking. Electrophysiological, structural and pathological aspects - as well as the autonomic control over the SAN - are taken into consideration to reach a holistic view of SAN activity.