{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:30:39Z","timestamp":1790836239117,"version":"4.1.0"},"reference-count":92,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T00:00:00Z","timestamp":1670025600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["PG\/14\/79\/31102"],"award-info":[{"award-number":["PG\/14\/79\/31102"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["PG\/19\/59\/34582"],"award-info":[{"award-number":["PG\/19\/59\/34582"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In cardiac myocytes, the voltage\u2010gated sodium channel Na<jats:sub>V<\/jats:sub>1.5 opens in response to membrane depolarisation and initiates the action potential. The Na<jats:sub>V<\/jats:sub>1.5 channel is typically associated with regulatory \u03b2\u2010subunits that modify gating and trafficking behaviour. These \u03b2\u2010subunits contain a single extracellular immunoglobulin (Ig) domain, a single transmembrane \u03b1\u2010helix and an intracellular region. Here we focus on the role of the \u03b21 and \u03b23 subunits in regulating Na<jats:sub>V<\/jats:sub>1.5. We catalogue \u03b21 and \u03b23 domain specific mutations that have been associated with inherited cardiac arrhythmia, including Brugada syndrome, long QT syndrome, atrial fibrillation and sudden death. We discuss how new structural insights into these proteins raises new questions about physiological function.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp15350-gra-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p>","DOI":"10.1113\/jp283085","type":"journal-article","created":{"date-parts":[[2022,11,10]],"date-time":"2022-11-10T15:10:33Z","timestamp":1668093033000},"page":"923-940","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Cardiac sodium channel complexes and arrhythmia: structural and functional roles of the \u03b21 and \u03b23 subunits"],"prefix":"10.1113","volume":"601","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5793-2349","authenticated-orcid":false,"given":"Samantha 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