{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T16:37:37Z","timestamp":1790354257812,"version":"4.1.0"},"reference-count":18,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T00:00:00Z","timestamp":1758844800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T00:00:00Z","timestamp":1758844800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["MOP-111072 and MOP-130373"],"award-info":[{"award-number":["MOP-111072 and MOP-130373"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-025-17816-2","type":"journal-article","created":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T11:03:28Z","timestamp":1758884608000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Biophysical and structural insights into the SCN4A E452K variant linked to myotonia and paramyotonia congenita"],"prefix":"10.1038","volume":"15","author":[{"given":"Quentin","family":"Plumereau","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Spencer","family":"Lile","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher N.","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Chahine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,9,26]]},"reference":[{"key":"17816_CR1","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1007\/BF02164912","volume":"6","author":"J Thomsen","year":"1876","unstructured":"Thomsen, J. Tonische Kr\u00e4mfe in willk\u00fcrlich beweglichen Musklen in Forge Von ererber psychischer Disposition. Arch. Psychiat. Nerukrankh. 6, 702 (1876).","journal-title":"Arch. Psychiat. Nerukrankh."},{"key":"17816_CR2","first-page":"1","volume":"9","author":"A Seeligm\u00fcller","year":"1886","unstructured":"Seeligm\u00fcller, A. Die Myotonie (Myotonia congenita). Dtsch. Z. Nervenheilkd. 9, 1\u201330 (1886).","journal-title":"Dtsch. Z. Nervenheilkd."},{"key":"17816_CR3","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.expneurol.2013.12.005","volume":"253","author":"JR Trivedi","year":"2014","unstructured":"Trivedi, J. R., Cannon, S. C. & Griggs, R. C. Nondystrophic myotonia: challenges and future directions. Exp. Neurol. 253, 28\u201330. https:\/\/doi.org\/10.1016\/j.expneurol.2013.12.005 (2014).","journal-title":"Exp. Neurol."},{"key":"17816_CR4","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1002\/mus.26887","volume":"62","author":"BC Stunnenberg","year":"2020","unstructured":"Stunnenberg, B. C. et al. Guidelines on clinical presentation and management of nondystrophic myotonias. Muscle Nerve. 62, 430\u2013444. https:\/\/doi.org\/10.1002\/mus.26887 (2020).","journal-title":"Muscle Nerve."},{"key":"17816_CR5","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1002\/cphy.c140062","volume":"5","author":"SC Cannon","year":"2015","unstructured":"Cannon, S. C. Channelopathies of skeletal muscle excitability. Compr. Physiol. 5, 761\u2013790. https:\/\/doi.org\/10.1002\/cphy.c140062 (2015).","journal-title":"Compr. Physiol."},{"key":"17816_CR6","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/0896-6273(94)90271-2","volume":"12","author":"M Chahine","year":"1994","unstructured":"Chahine, M. et al. Sodium channel mutations in paramyotonia congenita uncouple inactivation from activation. Neuron 12, 281\u2013294 (1994).","journal-title":"Neuron"},{"key":"17816_CR7","first-page":"A4","volume":"64","author":"M Chahine","year":"1993","unstructured":"Chahine, M., Bennett, P. B., Horn, R. & George, A. L. Functional expression of the human skeletal muscle sodium channel. Biophys. J. 64, A4 (1993).","journal-title":"Biophys. J."},{"key":"17816_CR8","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1007\/s00424-010-0814-4","volume":"460","author":"K Jurkat-Rott","year":"2010","unstructured":"Jurkat-Rott, K., Holzherr, B., Fauler, M. & Lehmann-Horn, F. Sodium channelopathies of skeletal muscle result from gain or loss of function. Pflugers Arch. 460, 239\u2013248. https:\/\/doi.org\/10.1007\/s00424-010-0814-4 (2010).","journal-title":"Pflugers Arch."},{"key":"17816_CR9","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1016\/j.nmd.2008.01.007","volume":"19","author":"N Dupr\u00e9","year":"2009","unstructured":"Dupr\u00e9, N. et al. Clinical, electrophysiologic, and genetic study of non-dystrophic myotonia in French-Canadians. Neuromuscul Disord. 19, 330\u2013334. https:\/\/doi.org\/10.1016\/j.nmd.2008.01.007 (2009).","journal-title":"Neuromuscul Disord."},{"key":"17816_CR10","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1016\/j.nmd.2018.03.006","volume":"28","author":"BC Stunnenberg","year":"2018","unstructured":"Stunnenberg, B. C. et al. Prevalence and mutation spectrum of skeletal muscle channelopathies in the Netherlands. Neuromuscul. Disord. 28, 402\u2013407. https:\/\/doi.org\/10.1016\/j.nmd.2018.03.006 (2018).","journal-title":"Neuromuscul. Disord."},{"key":"17816_CR11","doi-asserted-by":"publisher","first-page":"1349","DOI":"10.1093\/hmg\/2.9.1349","volume":"2","author":"R Heine","year":"1993","unstructured":"Heine, R., Pika, U. & Lehmann-Horn, F. A novel SCN4A mutation causing myotonia aggravated by cold and potassium. Hum. Mol. Genet. 2, 1349\u20131353 (1993).","journal-title":"Hum. Mol. Genet."},{"key":"17816_CR12","doi-asserted-by":"publisher","first-page":"1095","DOI":"10.1001\/archneur.1994.00540230033009","volume":"51","author":"K Ricker","year":"1994","unstructured":"Ricker, K., Moxley, R. T. III., Heine, R. & Lehmann-Horn, F. Myotonia fluctuans. A third type of muscle sodium channel disease. Arch. Neurol. 51, 1095\u20131102 (1994).","journal-title":"Arch. Neurol."},{"key":"17816_CR13","doi-asserted-by":"publisher","first-page":"666","DOI":"10.1002\/mus.21155","volume":"39","author":"T Kubota","year":"2009","unstructured":"Kubota, T. et al. New mutation of the Na channel in the severe form of potassium-aggravated myotonia. Muscle Nerve. 39, 666\u2013673. https:\/\/doi.org\/10.1002\/mus.21155 (2009).","journal-title":"Muscle Nerve."},{"key":"17816_CR14","doi-asserted-by":"publisher","DOI":"10.1126\/science.aau2486","author":"X Pan","year":"2018","unstructured":"Pan, X. et al. Structure of the human voltage-gated sodium channel Na(v)14 in complex with \u03b21. Science https:\/\/doi.org\/10.1126\/science.aau2486 (2018).","journal-title":"Science"},{"key":"17816_CR15","doi-asserted-by":"publisher","first-page":"528","DOI":"10.1021\/acs.jctc.9b00591","volume":"16","author":"C Tian","year":"2020","unstructured":"Tian, C. et al. ff19SB: Amino-acid-specific protein backbone parameters trained against quantum mechanics energy surfaces in solution. J. Chem. Theory Comput. 16, 528\u2013552. https:\/\/doi.org\/10.1021\/acs.jctc.9b00591 (2020).","journal-title":"J. Chem. Theory Comput."},{"key":"17816_CR16","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1016\/j.phrs.2019.01.004","volume":"141","author":"A Farinato","year":"2019","unstructured":"Farinato, A. et al. Pharmacogenetics of myotonic hNav1.4 sodium channel variants situated near the fast inactivation gate. Pharmacol. Res. 141, 224\u2013235. https:\/\/doi.org\/10.1016\/j.phrs.2019.01.004 (2019).","journal-title":"Pharmacol. Res."},{"key":"17816_CR17","doi-asserted-by":"publisher","first-page":"H288","DOI":"10.1152\/ajpheart.00539.2010","volume":"300","author":"H Huang","year":"2011","unstructured":"Huang, H., Priori, S. G., Napolitano, C., O\u2019Leary, M. E. & Chahine, M. Y1767C, a novel SCN5A mutation, induces a persistent Na+ current and potentiates ranolazine inhibition of Nav1.5 channels. Am. J. Physiol. Heart Circ. Physiol. 300, H288-299. https:\/\/doi.org\/10.1152\/ajpheart.00539.2010 (2011).","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"17816_CR18","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1016\/j.cjco.2020.09.023","volume":"3","author":"Q Plumereau","year":"2021","unstructured":"Plumereau, Q. et al. Novel G1481V and Q1491H SCN5A mutations linked to long QT syndrome destabilize the Nav1.5 inactivation state. CJC Open 3, 256\u2013266. https:\/\/doi.org\/10.1016\/j.cjco.2020.09.023 (2021).","journal-title":"CJC Open"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-17816-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-17816-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-17816-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T11:03:29Z","timestamp":1758884609000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-17816-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,26]]},"references-count":18,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["17816"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-17816-2","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,26]]},"assertion":[{"value":"14 April 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 August 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 September 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"33101"}}