title: Biophysical phenotypes of SCN5A mutations causing long QT and Brugada syndromes.
abstract: Long QT and Brugada syndromes are two hereditary cardiac diseases. Brugada syndrome has so far been associated with only one gene, SCN5A, which encodes the cardiac sodium channel. However, in long QT syndrome (LQTS) at least six genes, including the SCN5A, are implicated. The substitution (D1790G) causes LQTS and the insertion (D1795) induces both LQTS and Brugada syndromes in carrier patients. hH1/insD1795 and hH1/D1790G mutant channels were expressed in the tsA201 human cell line and characterized using the patch clamp technique in whole-cell configuration. Our data revealed a persistent inward sodium current of about 6% at -30 mV for both D1790G and insD1795, and a reduction of 62% of channel expression for the insD1795. Moreover, a shift of steady-state inactivation curve in both mutants was also observed. Our findings uphold the idea that LQT3 is related to a persistent sodium current whereas reduction in the expression level of cardiac sodium channels is one of the biophysical characteristics of Brugada syndrome.
authors.affiliation: Laval University, Department of Medicine, Canada.
authors.forename: G
authors.initials: G
authors.lastname: Baroudi
authors.forename: M
authors.initials: M
authors.lastname: Chahine
mesh_terms: D019943:Amino Acid Substitution; D002037:Bundle-Branch Block / Q000235:genetics*; D002460:Cell Line; D016757:Death, Sudden, Cardiac; D004569:Electroencephalography; D006580:Genetic Carrier Screening; D006801:Humans; D007668:Kidney; D008133:Long QT Syndrome / Q000235:genetics*; D008564:Membrane Potentials; D016297:Mutagenesis, Site-Directed; D020125:Mutation, Missense; D062554:NAV1.5 Voltage-Gated Sodium Channel; D021122:Protein Subunits; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D015222:Sodium Channels / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D013577:Syndrome; D014162:Transfection
chemical_list: D062554:NAV1.5 Voltage-Gated Sodium Channel; D021122:Protein Subunits; D011994:Recombinant Proteins; C568320:SCN5A protein, human; D015222:Sodium Channels