IndraLab

"Mutations in SCN5A, a cardiac sodium channel gene, have been recently associated with Brugada syndrome."

"Direct Ca 2+ binding to hH1 domain of sodium channel was shown to induce a rightward shift in the steady state inactivation increasing the availability of channels at more positive potentials [ xref ], therefore buffering cytosolic Ca 2+ should reduce Na + current."

"Brugada syndrome has so far been associated with only one gene, SCN5A, which encodes the cardiac sodium channel."

"Furthermore, mutations in the SCN5A sodium channel gene have been associated with an increased risk of arrhythmic events xref ."

"Preliminary reports indicate an important association with SCN10A , a neuronal sodium channel that co-associates with SCN5A, with a yield as high as 20%."

"Mutations in SCN5A, the cardiac sodium channel gene, are associated with varied arrhythmia phenotypes, e.g. long QT syndrome (LQTS), Brugada syndrome (BrS), sick sinus syndrome (SSS), progressive atrioventricular (AV) conduction system disease, ventricular fibrillation and dilated cardiomyopathy. xref Although these arrhythmia phenotypes were originally considered distinct entities, overlap in the clinical presentation has been frequently noted. xref – xref The clinical heterogeneity associated with SCN5A mutations is partly explained by corresponding differences in the degree and characteristics of sodium channel dysfunction."

"Scn5a, which forms the actual pore of the VGSC, is sufficient to enhance this ligand sensitivity in the absence of Scn4b, which serves as a modifier of the electrophysiological properties of the channel."

"In patients, deletions or loss-of-function mutations of the cardiac sodium channel gene, SCN5A, have been associated with a wide range of arrhythmias including bradycardia (heart rate slowing), atrioventricular conduction delay, and ventricular fibrillation."