IndraLab

"Drugs exhibit diverse binding modes and access routes in the Nav1.5 cardiac sodium channel pore."

"The slow conduction properties of nodal tissue are determined by the near absence of the cardiac sodium channel pore forming subunit NaV1.5 (encoded by Scn5a ) and the preferential expression of low conductance gap junction proteins Cx30.2 and Cx45 (encoded by Gjd3 and Gja7 , respectively)."

"Our results seem to indicate that the wild-type genotype for SNV rs2298771 in SCN1A , which encodes the voltage-gated sodium channel—NaV1.1 sodium channel alpha subunit—results in a loss-of-function protein presenting a lower expression, with an insufficiency of NaV1.1, as observed in the SCN1A gene mutated in Dravet Syndrome, as well as milder phenotypes associated with genetic epilepsy with febrile seizures plus [ xref , xref , xref ]."

"The sodium channel (SCN) 5A gene, located on human chromosome 3p22, is responsible for producing the α subunit Nav1.5, which forms the pore of the cardiac sodium channel."

"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."

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

"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."

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

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

"In BrS, VF is a result of complex interactions between genetic mutations in the SCN5A gene, leading to reduced sodium channel function and unique electrophysiological properties of the right ventricular epicardium, which has a large I to ."

"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."

"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."