{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T19:56:58Z","timestamp":1791143818448,"version":"4.1.0"},"reference-count":28,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2001,6,22]]},"abstract":"<jats:p>\n            <jats:italic>Abstract<\/jats:italic>\n            \u2014The\n            <jats:italic>SCN5A<\/jats:italic>\n            gene encodes the \u03b1 subunit of the human heart sodium channel (hH1), which plays a critical role in cardiac excitability. Mutations of\n            <jats:italic>SCN5A<\/jats:italic>\n            underlie Brugada syndrome, an inherited disorder that leads to ventricular fibrillation and sudden death. This study describes changes in cellular localization and functional expression of hH1 in a naturally occurring\n            <jats:italic>SCN5A<\/jats:italic>\n            mutation (R1432G) reported for Brugada syndrome. Using patch-clamp experiments, we show that there is an abolition of functional hH1 expression in R1432G mutants expressed in human tsA201 cells but not in\n            <jats:italic>Xenopus<\/jats:italic>\n            oocytes. In tsA201 cells, a conservative positively charged mutant, R1432K, produced sodium currents with normal gating properties, whereas other mutations at this site abolished functional sodium channel expression. Immunofluorescent staining and confocal microscopy showed that the wild-type \u03b1 subunit expressed in tsA201 cells was localized to the cell surface, whereas the R1432G mutant was colocalized with calnexin within the endoplasmic reticulum. The \u03b2\n            <jats:sub>1<\/jats:sub>\n            subunit was also localized to the cell surface in the presence of the \u03b1 subunit; however, in its absence, the \u03b2\n            <jats:sub>1<\/jats:sub>\n            subunit was restricted to a perinuclear localization. These results demonstrate that the disruption of\n            <jats:italic>SCN5A<\/jats:italic>\n            cell-surface localization is one mechanism that can account for the loss of functional sodium channels in Brugada syndrome. The full text of this article is available at http:\/\/www.circresaha.org.\n          <\/jats:p>","DOI":"10.1161\/hh1201.093270","type":"journal-article","created":{"date-parts":[[2007,9,28]],"date-time":"2007-09-28T18:32:49Z","timestamp":1191004369000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":96,"title":["Novel Mechanism for Brugada Syndrome"],"prefix":"10.1161","volume":"88","author":[{"given":"Ghayath","family":"Baroudi","sequence":"first","affiliation":[{"name":"From Laval University, Department of Medicine (G.B., V.P., M.C.) and Que\u0301bec Heart Institute, Laval Hospital, Research Center (G.B., V.P., M.C.), Sainte-Foy, Que\u0301bec, Canada; Service de Cardiologie, Ho\u0302pital Lariboisie\u0300re (I.D.) and INSERM U523, Institut de Myologie, IFR \u201cC\u0153ur, muscles et vaisseaux\u201d No. 14, Groupe hospitalier Pitie\u0301-Salpe\u0302trie\u0300re (P.G.), Paris, France; and Department of Physiology, McGill University (A.S.), Montreal, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie","family":"Pouliot","sequence":"additional","affiliation":[{"name":"From Laval University, Department of Medicine (G.B., V.P., M.C.) and Que\u0301bec Heart Institute, Laval Hospital, Research Center (G.B., V.P., M.C.), Sainte-Foy, Que\u0301bec, Canada; Service de Cardiologie, Ho\u0302pital Lariboisie\u0300re (I.D.) and INSERM U523, Institut de Myologie, IFR \u201cC\u0153ur, muscles et vaisseaux\u201d No. 14, Groupe hospitalier Pitie\u0301-Salpe\u0302trie\u0300re (P.G.), Paris, France; and Department of Physiology, McGill University (A.S.), Montreal, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Denjoy","sequence":"additional","affiliation":[{"name":"From Laval University, Department of Medicine (G.B., V.P., M.C.) and Que\u0301bec Heart Institute, Laval Hospital, Research Center (G.B., V.P., M.C.), Sainte-Foy, Que\u0301bec, Canada; Service de Cardiologie, Ho\u0302pital Lariboisie\u0300re (I.D.) and INSERM U523, Institut de Myologie, IFR \u201cC\u0153ur, muscles et vaisseaux\u201d No. 14, Groupe hospitalier Pitie\u0301-Salpe\u0302trie\u0300re (P.G.), Paris, France; and Department of Physiology, McGill University (A.S.), Montreal, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascale","family":"Guicheney","sequence":"additional","affiliation":[{"name":"From Laval University, Department of Medicine (G.B., V.P., M.C.) and Que\u0301bec Heart Institute, Laval Hospital, Research Center (G.B., V.P., M.C.), Sainte-Foy, Que\u0301bec, Canada; Service de Cardiologie, Ho\u0302pital Lariboisie\u0300re (I.D.) and INSERM U523, Institut de Myologie, IFR \u201cC\u0153ur, muscles et vaisseaux\u201d No. 14, Groupe hospitalier Pitie\u0301-Salpe\u0302trie\u0300re (P.G.), Paris, France; and Department of Physiology, McGill University (A.S.), Montreal, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alvin","family":"Shrier","sequence":"additional","affiliation":[{"name":"From Laval University, Department of Medicine (G.B., V.P., M.C.) and Que\u0301bec Heart Institute, Laval Hospital, Research Center (G.B., V.P., M.C.), Sainte-Foy, Que\u0301bec, Canada; Service de Cardiologie, Ho\u0302pital Lariboisie\u0300re (I.D.) and INSERM U523, Institut de Myologie, IFR \u201cC\u0153ur, muscles et vaisseaux\u201d No. 14, Groupe hospitalier Pitie\u0301-Salpe\u0302trie\u0300re (P.G.), Paris, France; and Department of Physiology, McGill University (A.S.), Montreal, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Chahine","sequence":"additional","affiliation":[{"name":"From Laval University, Department of Medicine (G.B., V.P., M.C.) and Que\u0301bec Heart Institute, Laval Hospital, Research Center (G.B., V.P., M.C.), Sainte-Foy, Que\u0301bec, Canada; Service de Cardiologie, Ho\u0302pital Lariboisie\u0300re (I.D.) and INSERM U523, Institut de Myologie, IFR \u201cC\u0153ur, muscles et vaisseaux\u201d No. 14, Groupe hospitalier Pitie\u0301-Salpe\u0302trie\u0300re (P.G.), Paris, France; and Department of Physiology, McGill University (A.S.), Montreal, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/0735-1097(92)90253-J"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.97.5.457"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.86.9.e91"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/32675"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2001.280.1.H354"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(00)00006-7"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(00)02360-7"},{"key":"e_1_3_2_8_2","doi-asserted-by":"crossref","unstructured":"Wang DW Makita N Kitabatake A Balser JR George AL Jr. Enhanced Na+ channel intermediate inactivation in Brugada syndrome. Circ Res.;2000;87:e37\u2013e43.","DOI":"10.1161\/01.RES.87.8.e37"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.85.9.872"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(00)01875-5"},{"key":"e_1_3_2_11_2","first-page":"876","volume":"17","year":"1994","unstructured":"Jurman ME, Boland LM, Liu Y, Yellen G. Visual identification of individual transfected cells for electrophysiology using antibody-coated beads. Biotechniques. 1994;17:876\u2013881.","journal-title":"Biotechniques"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(00)01099-1"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(86)90664-1"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)91013-6"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00388a029"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/46045"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.44.31123"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.99.17.2290"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/358761a0"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1999.79.1.S167"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.2000.278.2.C259"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1999.041ad.x"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/8.8.1499"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0223(199605)16:5<458::AID-PD873>3.0.CO;2-U"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.3513311"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI2303"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.2000.279.4.H1748"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2000.4139"}],"container-title":["Circulation Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/hh1201.093270","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T02:25:16Z","timestamp":1715653516000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/hh1201.093270"}},"subtitle":["Defective Surface Localization of an\n            <i>SCN5A<\/i>\n            Mutant (R1432G)"],"short-title":[],"issued":{"date-parts":[[2001,6,22]]},"references-count":28,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2001,6,22]]}},"alternative-id":["10.1161\/hh1201.093270"],"URL":"https:\/\/doi.org\/10.1161\/hh1201.093270","relation":{},"ISSN":["0009-7330","1524-4571"],"issn-type":[{"value":"0009-7330","type":"print"},{"value":"1524-4571","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,6,22]]},"assertion":[{"value":"2001-06-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}