Dominant-negative effect of SCN5A N-terminal mutations through the interaction of Na(v)1.5 α-subunits.

ABSTRACT:

Aims

Brugada syndrome (BrS) is an autosomal-inherited cardiac arrhythmia characterized by an ST-segment elevation in the right precordial leads of the electrocardiogram and an increased risk of syncope and sudden death. SCN5A, encoding the cardiac sodium channel Na(v)1.5, is the main gene involved in BrS. Despite the fact that several mutations have been reported in the N-terminus of Na(v)1.5, the functional role of this region remains unknown. We aimed to characterize two BrS N-terminal mutations, R104W and R121W, a construct where this region was deleted, ΔNter, and a construct where only this region was present, Nter.

Methods and results

Patch-clamp recordings in HEK293 cells demonstrated that R104W, R121W, and ΔNter abolished the sodium current I(Na). Moreover, R104W and

SUBMITTER: Clatot J 

PROVIDER: S-EPMC3444234 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature