| http://purl.uniprot.org/citations/12673799 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/12673799 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/12673799 | http://www.w3.org/2000/01/rdf-schema#comment | "Congenital long QT syndrome type 3 (LQT3) is caused by mutations in the gene SCN5A encoding the alpha-subunit of the cardiac Na(+) channel (Nav1.5). Functional studies of SCN5A mutations in the linker between domains III and IV, and more recently the C-terminus, have been shown to alter inactivation gating. Here we report a novel LQT3 mutation, L619F (LF), located in the domain I-II linker. In an infant with prolonged QTc intervals, mutational analysis identified a heterozygous missense mutation (L619F) in the domain I-II linker of the cardiac Na(+) channel. Wild-type (WT) and mutant channels were studied by whole-cell patch-clamp analysis in transiently expressed HEK cells. LF channels increase maintained Na(+) current (0.79 pA/pF for LF; 0.26 pA/pF for WT) during prolonged depolarization. We found a +5.8mV shift in steady state inactivation in LF channels compared to WT (WT, V(1/2)=-64.0 mV; LF, V(1/2)=-58.2 mV). The positive shift of inactivation, without a corresponding shift in activation, increases the overlap window current in LF relative to WT (1.09 vs. 0.58 pA/pF), as measured using a positive voltage ramp protocol (-100 to +50 mV in 2s). The increase in window current, combined with an increase in non-inactivating Na(+) current, may act to prolong the AP plateau and is consistent with the disease phenotype observed in patients. Moreover, the defective inactivation imposed by the L619F mutation implies a role for the I-II linker in the Na(+) channel inactivation process."xsd:string |
| http://purl.uniprot.org/citations/12673799 | http://purl.org/dc/terms/identifier | "doi:10.1002/humu.9136"xsd:string |
| http://purl.uniprot.org/citations/12673799 | http://purl.org/dc/terms/identifier | "doi:10.1002/humu.9136"xsd:string |
| http://purl.uniprot.org/citations/12673799 | http://purl.uniprot.org/core/author | "Kass R.S."xsd:string |
| http://purl.uniprot.org/citations/12673799 | http://purl.uniprot.org/core/author | "Kass R.S."xsd:string |
| http://purl.uniprot.org/citations/12673799 | http://purl.uniprot.org/core/author | "Gewillig M."xsd:string |
| http://purl.uniprot.org/citations/12673799 | http://purl.uniprot.org/core/author | "Gewillig M."xsd:string |
| http://purl.uniprot.org/citations/12673799 | http://purl.uniprot.org/core/author | "Vos M.A."xsd:string |
| http://purl.uniprot.org/citations/12673799 | http://purl.uniprot.org/core/author | "Vos M.A."xsd:string |
| http://purl.uniprot.org/citations/12673799 | http://purl.uniprot.org/core/author | "Wehrens X.H."xsd:string |
| http://purl.uniprot.org/citations/12673799 | http://purl.uniprot.org/core/author | "Wehrens X.H."xsd:string |
| http://purl.uniprot.org/citations/12673799 | http://purl.uniprot.org/core/author | "Jongbloed R.J."xsd:string |
| http://purl.uniprot.org/citations/12673799 | http://purl.uniprot.org/core/author | "Jongbloed R.J."xsd:string |
| http://purl.uniprot.org/citations/12673799 | http://purl.uniprot.org/core/author | "Wellens H.J."xsd:string |
| http://purl.uniprot.org/citations/12673799 | http://purl.uniprot.org/core/author | "Wellens H.J."xsd:string |
| http://purl.uniprot.org/citations/12673799 | http://purl.uniprot.org/core/author | "Doevendans P.A."xsd:string |
| http://purl.uniprot.org/citations/12673799 | http://purl.uniprot.org/core/author | "Doevendans P.A."xsd:string |
| http://purl.uniprot.org/citations/12673799 | http://purl.uniprot.org/core/author | "Heidbuchel H."xsd:string |
| http://purl.uniprot.org/citations/12673799 | http://purl.uniprot.org/core/author | "Heidbuchel H."xsd:string |
| http://purl.uniprot.org/citations/12673799 | http://purl.uniprot.org/core/author | "Rossenbacker T."xsd:string |
| http://purl.uniprot.org/citations/12673799 | http://purl.uniprot.org/core/author | "Rossenbacker T."xsd:string |
| http://purl.uniprot.org/citations/12673799 | http://purl.uniprot.org/core/date | "2003"xsd:gYear |
| http://purl.uniprot.org/citations/12673799 | http://purl.uniprot.org/core/date | "2003"xsd:gYear |