{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T16:37:03Z","timestamp":1790354223979,"version":"4.1.0"},"reference-count":49,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2022,11,22]],"date-time":"2022-11-22T00:00:00Z","timestamp":1669075200000},"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":["R01HL112808 to WAC and NZ, R35NS111573 to WAC"],"award-info":[{"award-number":["R01HL112808 to WAC and NZ, R35NS111573 to WAC"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Nav1.5 is the main voltage-gated sodium channel found in cardiac muscle, where it facilitates the fast influx of Na+ ions across the cell membrane, resulting in the fast depolarization phase\u2014phase 0 of the cardiac action potential. As a result, it plays a major role in determining the amplitude and the upstroke velocity of the cardiac impulse. Quantitively, cardiac sodium channel activates in less than a millisecond to trigger the cardiac action potential and inactivates within 2\u20133 ms to facilitate repolarization and return to the resting state in preparation for firing the next action potential. Missense mutations in the gene that encodes Nav1.5 (SCN5A), change these time constants which leads to a wide spectrum of cardiac diseases ranging from long QT syndrome type 3 (LQT3) to sudden cardiac death. In this mini-review I will focus on the missense mutations in the inactivation gate of Nav1.5 that results in arrhythmia, attempting to correlate the location of the missense mutation to their specific phenotype.<\/jats:p>","DOI":"10.3390\/cells11233714","type":"journal-article","created":{"date-parts":[[2022,11,22]],"date-time":"2022-11-22T08:27:29Z","timestamp":1669105649000},"page":"3714","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["When the Gates Swing Open Only: Arrhythmia Mutations That Target the Fast Inactivation Gate of Nav1.5"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7406-7393","authenticated-orcid":false,"given":"Tamer M.","family":"Gamal El-Din","sequence":"first","affiliation":[{"name":"Department of Pharmacology, University of Washington, Seattle, WA 98195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1146\/annurev-pharmtox-010818-021757","article-title":"Structure and Pharmacology of Voltage-Gated Sodium and Calcium Channels","volume":"60","author":"Catterall","year":"2020","journal-title":"Annu. 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