{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T06:18:18Z","timestamp":1762409898791,"version":"build-2065373602"},"reference-count":84,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,4,29]],"date-time":"2021-04-29T00:00:00Z","timestamp":1619654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01\u2010HL135096, R01HL134824, R01\u2010HL156652"],"award-info":[{"award-number":["R01\u2010HL135096, R01HL134824, R01\u2010HL156652"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCDD"],"abstract":"<jats:p>The cardiac conduction system is an extended network of excitable tissue tasked with generation and propagation of electrical impulses to signal coordinated contraction of the heart. The fidelity of this system depends on the proper spatio-temporal regulation of ion channels in myocytes throughout the conduction system. Importantly, inherited or acquired defects in a wide class of ion channels has been linked to dysfunction at various stages of the conduction system resulting in life-threatening cardiac arrhythmia. There is growing appreciation of the role that adapter and cytoskeletal proteins play in organizing ion channel macromolecular complexes critical for proper function of the cardiac conduction system. In particular, members of the ankyrin and spectrin families have emerged as important nodes for normal expression and regulation of ion channels in myocytes throughout the conduction system. Human variants impacting ankyrin\/spectrin function give rise to a broad constellation of cardiac arrhythmias. Furthermore, chronic neurohumoral and biomechanical stress promotes ankyrin\/spectrin loss of function that likely contributes to conduction disturbances in the setting of acquired cardiac disease. Collectively, this review seeks to bring attention to the significance of these cytoskeletal players and emphasize the potential therapeutic role they represent in a myriad of cardiac disease states.<\/jats:p>","DOI":"10.3390\/jcdd8050048","type":"journal-article","created":{"date-parts":[[2021,4,29]],"date-time":"2021-04-29T04:30:11Z","timestamp":1619670611000},"page":"48","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Regulation of Cardiac Conduction and Arrhythmias by Ankyrin\/Spectrin-Based Macromolecular Complexes"],"prefix":"10.3390","volume":"8","author":[{"given":"Drew","family":"Nassal","sequence":"first","affiliation":[{"name":"The Frick Center for Heart Failure and Arrhythmia, The Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA"},{"name":"Department of Biomedical Engineering, College of Engineering, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jane","family":"Yu","sequence":"additional","affiliation":[{"name":"The Frick Center for Heart Failure and Arrhythmia, The Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA"},{"name":"Department of Biomedical Engineering, College of Engineering, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dennison","family":"Min","sequence":"additional","affiliation":[{"name":"The Frick Center for Heart Failure and Arrhythmia, The Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA"},{"name":"Department of Biomedical Engineering, College of Engineering, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cemantha","family":"Lane","sequence":"additional","affiliation":[{"name":"The Frick Center for Heart Failure and Arrhythmia, The Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA"},{"name":"Department of Biomedical Engineering, College of Engineering, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca","family":"Shaheen","sequence":"additional","affiliation":[{"name":"The Frick Center for Heart Failure and Arrhythmia, The Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA"},{"name":"Department of Biomedical Engineering, College of Engineering, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Gratz","sequence":"additional","affiliation":[{"name":"The Frick Center for Heart Failure and Arrhythmia, The Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA"},{"name":"Department of Biomedical Engineering, College of Engineering, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas J.","family":"Hund","sequence":"additional","affiliation":[{"name":"The Frick Center for Heart Failure and Arrhythmia, The Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA"},{"name":"Department of Biomedical Engineering, College of Engineering, The Ohio State University, Columbus, OH 43210, USA"},{"name":"Department of Internal Medicine, College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"ii1","DOI":"10.1093\/europace\/eux258","article-title":"A decade of information on the use of cardiac implantable electronic devices and interventional electrophysiological procedures in the European Society of Cardiology Countries: 2017 report from the European Heart Rhythm Association","volume":"19","author":"Raatikainen","year":"2017","journal-title":"Europace"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/j.pharmthera.2013.04.010","article-title":"Structure, function and clinical relevance of the cardiac conduction system, including the atrioventricular ring and outflow tract tissues","volume":"139","author":"Dobrzynski","year":"2013","journal-title":"Pharmacol. 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