| http://purl.uniprot.org/citations/11304498 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/11304498 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/11304498 | http://www.w3.org/2000/01/rdf-schema#comment | "Variant 3 of the congenital long-QT syndrome (LQTS-3) is caused by mutations in the gene encoding the alpha subunit of the cardiac Na(+) channel. In the present study, we report a novel LQTS-3 mutation, E1295K (EK), and describe its functional consequences when expressed in HEK293 cells. The clinical phenotype of the proband indicated QT interval prolongation in the absence of T-wave morphological abnormalities and a steep QT/R-R relationship, consistent with an LQTS-3 lesion. However, biophysical analysis of mutant channels indicates that the EK mutation changes channel activity in a manner that is distinct from previously investigated LQTS-3 mutations. The EK mutation causes significant positive shifts in the half-maximal voltage (V(1/2)) of steady-state inactivation and activation (+5.2 and +3.4 mV, respectively). These gating changes shift the window of voltages over which Na(+) channels do not completely inactivate without altering the magnitude of these currents. The change in voltage dependence of window currents suggests that this alteration in the voltage dependence of Na(+) channel gating may cause marked changes in action potential duration because of the unique voltage-dependent rectifying properties of cardiac K(+) channels that underlie the plateau and terminal repolarization phases of the action potential. Na(+) channel window current is likely to have a greater effect on net membrane current at more positive potentials (EK channels) where total K(+) channel conductance is low than at more negative potentials (wild-type channels), where total K(+) channel conductance is high. These findings suggest a fundamentally distinct mechanism of arrhythmogenesis for congenital LQTS-3."xsd:string |
| http://purl.uniprot.org/citations/11304498 | http://purl.org/dc/terms/identifier | "doi:10.1161/hh0701.089668"xsd:string |
| http://purl.uniprot.org/citations/11304498 | http://purl.org/dc/terms/identifier | "doi:10.1161/hh0701.089668"xsd:string |
| http://purl.uniprot.org/citations/11304498 | http://purl.uniprot.org/core/author | "Abriel H."xsd:string |
| http://purl.uniprot.org/citations/11304498 | http://purl.uniprot.org/core/author | "Abriel H."xsd:string |
| http://purl.uniprot.org/citations/11304498 | http://purl.uniprot.org/core/author | "Kass R.S."xsd:string |
| http://purl.uniprot.org/citations/11304498 | http://purl.uniprot.org/core/author | "Kass R.S."xsd:string |
| http://purl.uniprot.org/citations/11304498 | http://purl.uniprot.org/core/author | "Napolitano C."xsd:string |
| http://purl.uniprot.org/citations/11304498 | http://purl.uniprot.org/core/author | "Napolitano C."xsd:string |
| http://purl.uniprot.org/citations/11304498 | http://purl.uniprot.org/core/author | "Priori S.G."xsd:string |
| http://purl.uniprot.org/citations/11304498 | http://purl.uniprot.org/core/author | "Priori S.G."xsd:string |
| http://purl.uniprot.org/citations/11304498 | http://purl.uniprot.org/core/author | "Rivolta I."xsd:string |
| http://purl.uniprot.org/citations/11304498 | http://purl.uniprot.org/core/author | "Rivolta I."xsd:string |
| http://purl.uniprot.org/citations/11304498 | http://purl.uniprot.org/core/author | "Memmi M."xsd:string |
| http://purl.uniprot.org/citations/11304498 | http://purl.uniprot.org/core/author | "Memmi M."xsd:string |
| http://purl.uniprot.org/citations/11304498 | http://purl.uniprot.org/core/author | "Wehrens X.H."xsd:string |
| http://purl.uniprot.org/citations/11304498 | http://purl.uniprot.org/core/author | "Wehrens X.H."xsd:string |
| http://purl.uniprot.org/citations/11304498 | http://purl.uniprot.org/core/author | "Cabo C."xsd:string |
| http://purl.uniprot.org/citations/11304498 | http://purl.uniprot.org/core/author | "Cabo C."xsd:string |
| http://purl.uniprot.org/citations/11304498 | http://purl.uniprot.org/core/author | "Motoike H.K."xsd:string |
| http://purl.uniprot.org/citations/11304498 | http://purl.uniprot.org/core/author | "Motoike H.K."xsd:string |
| http://purl.uniprot.org/citations/11304498 | http://purl.uniprot.org/core/date | "2001"xsd:gYear |
| http://purl.uniprot.org/citations/11304498 | http://purl.uniprot.org/core/date | "2001"xsd:gYear |