Unknown

Dataset Information

0

Embryonic type Na+ channel ?-subunit, SCN3B masks the disease phenotype of Brugada syndrome.

ABSTRACT: SCN5A is abundant in heart and has a major role in INa. Loss-of-function mutation in SCN5A results in Brugada syndrome (BrS), which causes sudden death in adults. It remains unclear why disease phenotype does not manifest in the young even though mutated SCN5A is expressed in the young. The aim of the present study is to elucidate the timing of the disease manifestation in BrS. A gain-of-function mutation in SCN5A also results in Long QT syndrome type 3 (LQTS3), leading to sudden death in the young. Induced pluripotent stem cells (iPSCs) were generated from a patient with a mixed phenotype of LQTS3 and BrS with the E1784K SCN5A mutation. Here we show that electrophysiological analysis revealed that LQTS3/BrS iPSC-derived cardiomyocytes recapitulate the phenotype of LQTS3 but not BrS. Each ?-subunit of the sodium channel is differentially expressed in embryonic and adult hearts. SCN3B is highly expressed in embryonic hearts and iPSC-derived cardiomyocytes. A heterologous expression system revealed that INa of mutated SCN5A is decreased and SCN3B augmented INa of mutated SCN5A. Knockdown of SCN3B in LQTS3/BrS iPSC-derived cardiomyocytes successfully unmasked the phenotype of BrS. Isogenic control of LQTS3/BrS (corrected-LQTS3/BrS) iPSC-derived cardiomyocytes gained the normal electrophysiological properties.

SUBMITTER: Okata S 

PROVIDER: S-EPMC5039759 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

SCN5A is abundant in heart and has a major role in I<sub>Na</sub>. Loss-of-function mutation in SCN5A results in Brugada syndrome (BrS), which causes sudden death in adults. It remains unclear why disease phenotype does not manifest in the young even though mutated SCN5A is expressed in the young. The aim of the present study is to elucidate the timing of the disease manifestation in BrS. A gain-of-function mutation in SCN5A also results in Long QT syndrome type 3 (LQTS3), leading to sudden deat  ...[more]

Similar Datasets

Unknown Specific decreasing of Na<sup>+</sup> channel expression on the lateral membrane of cardiomyocytes causes fatal arrhythmias in Brugada syndrome.
| S-EPMC7673036 | biostudies-literature
Unknown Brugada syndrome disease phenotype explained in apparently benign sodium channel mutations.
| S-EPMC3989843 | biostudies-literature
Unknown Sodium channel β1 subunit mutations associated with Brugada syndrome and cardiac conduction disease in humans.
| S-EPMC2373423 | biostudies-literature
Unknown A mutation in the beta 3 subunit of the cardiac sodium channel associated with Brugada ECG phenotype.
| S-EPMC2801870 | biostudies-literature
Unknown Na(+) channel mutation that causes both Brugada and long-QT syndrome phenotypes: a simulation study of mechanism.
| S-EPMC1997279 | biostudies-literature
Unknown Relationship between sodium channel function and clinical phenotype in SCN5A variants associated with Brugada syndrome.
| S-EPMC7756571 | biostudies-literature
Unknown Dysfunction of the Voltage-Gated K+ Channel β2 Subunit in a Familial Case of Brugada Syndrome.
| S-EPMC4937261 | biostudies-literature
Unknown Brugada syndrome genetics is associated with phenotype severity.
| S-EPMC7955973 | biostudies-literature
Unknown Enhanced Classification of Brugada Syndrome-Associated and Long-QT Syndrome-Associated Genetic Variants in the SCN5A-Encoded Na(v)1.5 Cardiac Sodium Channel.
| S-EPMC4878676 | biostudies-literature
Unknown A consistent arrhythmogenic trait in Brugada syndrome cellular phenotype.
| S-EPMC8181201 | biostudies-literature