Role of sinoatrial node architecture in maintaining a balanced source-sink relationship and synchronous cardiac pacemaking
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). Howe...
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Published in | Frontiers in physiology Vol. 5; p. 446 |
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Format | Journal Article |
Language | English |
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26.11.2014
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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. |
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AbstractList | 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. |
Author | Hund, Thomas J Wolf, Roseanne M Unudurthi, Sathya D |
AuthorAffiliation | 1 Department of Biomedical Engineering, College of Engineering, The Ohio State University Columbus, OH, USA 2 The Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center Columbus, OH, USA 3 Department of Mathematics, The University of Dubuque Dubuque, IA, USA 4 Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University Wexner Medical Center Columbus, OH, USA |
AuthorAffiliation_xml | – name: 3 Department of Mathematics, The University of Dubuque Dubuque, IA, USA – name: 4 Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University Wexner Medical Center Columbus, OH, USA – name: 1 Department of Biomedical Engineering, College of Engineering, The Ohio State University Columbus, OH, USA – name: 2 The Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center Columbus, OH, USA |
Author_xml | – sequence: 1 givenname: Sathya D surname: Unudurthi fullname: Unudurthi, Sathya D organization: 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 – sequence: 2 givenname: Roseanne M surname: Wolf fullname: Wolf, Roseanne M organization: Department of Mathematics, The University of Dubuque Dubuque, IA, USA – sequence: 3 givenname: Thomas J surname: Hund fullname: Hund, Thomas J organization: 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 |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/25505419$$D View this record in MEDLINE/PubMed |
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Keywords | source-sink relationship arrhythmia intercellular coupling sinoatrial node pacemaking sick sinus syndrome automaticity |
Language | English |
License | This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
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Notes | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-3 content type line 23 ObjectType-Review-1 This article was submitted to Cardiac Electrophysiology, a section of the journal Frontiers in Physiology. Edited by: George E. Billman, The Ohio State University, USA Reviewed by: Raimond L. Winslow, The Johns Hopkins University, USA; Crystal M. Ripplinger, University of California, Davis, USA |
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SubjectTerms | arrhythmia automaticity electrical coupling pacemaking Physiology Sick Sinus Syndrome Sinoatrial Node |
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Title | Role of sinoatrial node architecture in maintaining a balanced source-sink relationship and synchronous cardiac pacemaking |
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