title: Role of sinoatrial node architecture in maintaining a balanced source-sink relationship and synchronous cardiac pacemaking.
abstract: Normal heart rhythm (sinus rhythm) depends on regular activity of the sinoatrial node (SAN), a heterogeneous collection of specialized myocytes in the right atrium. SAN cells, in general, possess a unique electrophysiological profile that promotes spontaneous electrical activity (automaticity). However, while automaticity is required for normal pacemaking, it is not necessarily sufficient. Less appreciated is the importance of the elaborate structure of the SAN complex for proper pacemaker function. Here, we review the important structural features of the SAN with a focus on how these elements help manage a precarious balance between electrical charge generated by the SAN ("source") and the charge needed to excite the surrounding atrial tissue ("sink"). We also discuss how compromised "source-sink" balance due, for example to fibrosis, may promote SAN dysfunction, characterized by slow and/or asynchronous pacemaker activity and even failure, in the setting of cardiovascular disease (e.g., heart failure, atrial fibrillation). Finally, we discuss implications of the "source-sink" balance in the SAN complex for cell and gene therapies aimed at creating a biological pacemaker as replacement or bridge to conventional electronic pacemakers.
authors.affiliation: Department of Biomedical Engineering, College of Engineering, The Ohio State University Columbus, OH, USA ; The Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center Columbus, OH, USA.
authors.forename: Sathya D
authors.initials: SD
authors.lastname: Unudurthi
authors.affiliation: Department of Mathematics, The University of Dubuque Dubuque, IA, USA.
authors.forename: Roseanne M
authors.initials: RM
authors.lastname: Wolf
authors.affiliation: Department of Biomedical Engineering, College of Engineering, The Ohio State University Columbus, OH, USA ; The Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center Columbus, OH, USA ; Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University Wexner Medical Center Columbus, OH, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Hund
keywords: arrhythmia; automaticity; intercellular coupling; pacemaking; sick sinus syndrome; sinoatrial node; source-sink relationship