Premium
Characterization of 2 Genetic Variants of Na v 1.5‐Arginine 689 Found in Patients with Cardiac Arrhythmias
Author(s) -
SOTTAS VALENTIN,
ROUGIER JEANSÉBASTIEN,
JOUSSET FLORIAN,
KUCERA JAN P.,
SHESTAK ANNA,
MAKAROV LEONID M.,
ZAKLYAZMINSKAYA ELENA V.,
ABRIEL HUGUES
Publication year - 2013
Publication title -
journal of cardiovascular electrophysiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.193
H-Index - 138
eISSN - 1540-8167
pISSN - 1045-3873
DOI - 10.1111/jce.12173
Subject(s) - medicine , sodium channel , sudden cardiac death , tetrodotoxin , long qt syndrome , arginine , cardiology , sodium , phenotype , gene , qt interval , amino acid , genetics , biology , chemistry , organic chemistry
Na v 1.5‐Arg689 in Arrhythmias Hundreds of genetic variants in SCN5A , the gene coding for the pore‐forming subunit of the cardiac sodium channel, Na v 1.5, have been described in patients with cardiac channelopathies as well as in individuals from control cohorts. The aim of this study was to characterize the biophysical properties of 2 naturally occurring Na v 1.5 variants, p.R689H and p.R689C, found in patients with cardiac arrhythmias and in control individuals. In addition, this study was motivated by the finding of the variant p.R689H in a family with sudden cardiac death (SCD) in children. When expressed in HEK293 cells, most of the sodium current (I Na ) biophysical properties of both variants were indistinguishable from the wild‐type (WT) channels. In both cases, however, an ∼2‐fold increase of the tetrodotoxin‐sensitive late I Na was observed. Action potential simulations and reconstruction of pseudo‐ECGs demonstrated that such a subtle increase in the late I Na may prolong the QT interval in a nonlinear fashion. In conclusion, despite the fact that the causality link between p.R689H and the phenotype of the studied family cannot be demonstrated, this study supports the notion that subtle alterations of Na v 1.5 variants may increase the risk for cardiac arrhythmias.