{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T14:27:28Z","timestamp":1777386448093,"version":"3.51.4"},"reference-count":40,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2018,8,30]],"date-time":"2018-08-30T00:00:00Z","timestamp":1535587200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81370285"],"award-info":[{"award-number":["81370285"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004000","name":"Guangzhou Science and Technology Program key projects","doi-asserted-by":"publisher","award":["201508020057"],"award-info":[{"award-number":["201508020057"]}],"id":[{"id":"10.13039\/501100004000","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2018,11]]},"abstract":"Abstract<\/jats:title>Background<\/jats:title>Abnormal cardiac ion channels current, including transient outward potassium current (Ito<\/jats:sub>), is associated with early repolarization syndrome (ERS<\/jats:styled-content>). Previous studies showed that mutations in SCN<\/jats:styled-content>1B\u03b2 both to increase the Ito<\/jats:sub> current and to decrease the sodium current. Yet its role in ERS<\/jats:styled-content> remains unknown.<\/jats:p><\/jats:sec>Objective<\/jats:title>To determine the role of mutations in the SCN<\/jats:styled-content>1B\u03b2 subunits in ERS<\/jats:styled-content>.<\/jats:p><\/jats:sec>Methods<\/jats:title>We screened for mutations in the SCN<\/jats:styled-content>1B genes from four families with ERS<\/jats:styled-content>. Wild\u2010type and mutant SCN<\/jats:styled-content>1B\u03b2 genes were co\u2010expressed with wild\u2010type KCND<\/jats:styled-content>3 in human embryonic kidney cells (HEK<\/jats:styled-content>293). Whole\u2010cell patch\u2010clamp technique and co\u2010immunoprecipitation were used to study the electrophysiological properties and explore the underlying mechanisms.<\/jats:p><\/jats:sec>Results<\/jats:title>S248R and R250T mutations in SCN<\/jats:styled-content>1B\u03b2 were detected in 4 families\u2019 probands. Neither S248R nor R250T mutation had significant influence on the sodium channel current density (IN<\/jats:sub><\/jats:styled-content>a<\/jats:sub>) when co\u2010expressed with SCN<\/jats:styled-content>5A\/WT<\/jats:styled-content>. Co\u2010expression of KCND<\/jats:styled-content>3\/WT<\/jats:styled-content> and SCN<\/jats:styled-content>1B\u03b2\/S248R or SCN<\/jats:styled-content>1B\u03b2\/R250T increased the transient outward potassium current Ito<\/jats:sub> by 27.44% and 199.89%, respectively (P\u00a0<\/jats:italic><\u00a0<\/jats:italic>0.05 and P\u00a0<\/jats:italic><\u00a0<\/jats:italic>0.01, respectively) when compared with SCN<\/jats:styled-content>1B\u03b2\/WT<\/jats:styled-content>. Electrophysiological properties showed that S248R and R250T mutations decreased the steady\u2010state inactivation and recovery from inactivation of Ito<\/jats:sub> channel. Co\u2010immunoprecipitation study demonstrated an increased association between SCN<\/jats:styled-content>1B\u03b2 mutations and Kv4.3 compared with SCN<\/jats:styled-content>1B\u03b2\/WT<\/jats:styled-content> (P\u00a0<\/jats:italic><\u00a0<\/jats:italic>0.05 and P\u00a0<\/jats:italic><\u00a0<\/jats:italic>0.01, respectively).<\/jats:p><\/jats:sec>Conclusion<\/jats:title>The S248R and R250T mutations of SCN<\/jats:styled-content>1B\u03b2 gene caused gain\u2010of\u2010function of Ito<\/jats:sub> by associated with Kv4.3, which maybe underlie the ERS<\/jats:styled-content> phenotype of the probands.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jcmm.13839","type":"journal-article","created":{"date-parts":[[2018,8,30]],"date-time":"2018-08-30T15:54:47Z","timestamp":1535644487000},"page":"5639-5647","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["SCN<\/scp>1B\u03b2 mutations that affect their association with Kv4.3 underlie early repolarization syndrome"],"prefix":"10.1111","volume":"22","author":[{"given":"Hao","family":"Yao","sequence":"first","affiliation":[{"name":"Department of Cardiology the First Affiliated Hospital Sun Yat\u2010Sen University and Key Laboratory on Assisted Circulation NHC Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Cardiology the First Affiliated Hospital Sun Yat\u2010Sen University and Key Laboratory on Assisted Circulation NHC Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yun\u2010Jiu","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Cardiology the First Affiliated Hospital Sun Yat\u2010Sen University and Key Laboratory on Assisted Circulation NHC Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xu\u2010Miao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cardiology the First Affiliated Hospital Sun Yat\u2010Sen University and Key Laboratory on Assisted Circulation NHC Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheng\u2010Cheng","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Cardiology the First Affiliated Hospital Sun Yat\u2010Sen University and Key Laboratory on Assisted Circulation NHC Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li\u2010Juan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cardiology the First Affiliated Hospital Sun Yat\u2010Sen University and Key Laboratory on Assisted Circulation NHC Guangzhou 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