title: SCN5A mutation (T1620M) causing Brugada syndrome exhibits different phenotypes when expressed in Xenopus oocytes and mammalian cells.
abstract: Brugada syndrome is a hereditary cardiac disease causing abnormal ST segment elevation in the ECG, right bundle branch block, ventricular fibrillation and sudden death. In this study we characterized a new mutation in the SCN5A gene (T1620M), causing the Brugada syndrome. The mutated channels were expressed in both Xenopus leavis oocytes and in mammalian tsA201 cells with and without the beta-subunit and studied using the patch clamp technique. Opposite phenotypes were observed depending on the expression system. T1620M mutation led to a faster recovery from inactivation and a shift of steady-state inactivation to more positive voltages when expressed in Xenopus oocytes. However, using the mammalian expression system no effect on steady-state inactivation was observed, but this mutation led to a slower recovery from inactivation. Our finding supports the idea that the slower recovery from inactivation of the cardiac sodium channels seen in our mammalian expression system could decrease the density of sodium channels during the cardiac cycle explaining the in vivo arrhythmogenesis in patients with Brugada syndrome.
authors.affiliation: Laval University, Department of Medicine, Sainte-Foy, Quebec, Canada.
authors.forename: G
authors.initials: G
authors.lastname: Baroudi
authors.forename: E
authors.initials: E
authors.lastname: Carbonneau
authors.forename: V
authors.initials: V
authors.lastname: Pouliot
authors.forename: M
authors.initials: M
authors.lastname: Chahine
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics*; D000818:Animals; D002460:Cell Line; D004553:Electric Conductivity; D015870:Gene Expression; D006801:Humans; D007700:Kinetics; D009154:Mutation / Q000235:genetics*; D009206:Myocardium; D062554:NAV1.5 Voltage-Gated Sodium Channel; D009865:Oocytes / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010641:Phenotype; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D013577:Syndrome; D014693:Ventricular Fibrillation / Q000151:congenital* / Q000235:genetics*; D014982:Xenopus laevis
chemical_list: D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human; D015222:Sodium Channels; D012964:Sodium