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Biophysical phenotypes of SCN5A mutations causing long QT and Brugada syndromes
Author(s) -
Baroudi Ghayath,
Chahine Mohamed
Publication year - 2000
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(00)02360-7
Subject(s) - brugada syndrome , phenotype , long qt syndrome , genetics , channelopathy , short qt syndrome , biology , medicine , qt interval , neuroscience , gene
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.