Functional analysis of novel SCN5A mutations related to Brugada syndrome

Abstract Brugada syndrome (BrS) is an arrhythmogenic disorder that has been linked to mutations in SCN5A, the gene encoding for pore-forming α-subunit of cardiac Na+ channel. Recently, novel SCN5A missense (A385T and R504T) were identified a BrS patient. Since are loop connecting transmembrane segments 5 6 domain 1 (S5-S6 DI) between 2 (DI-DII linker), it can lead dysfunctional property Here we aimed characterize electrophysiological properties A385T R504T. The wild-type (WT) mutant transiently transfected HEK293 cells, channel was analyzed using whole-cell patch-clamp technique. WT, A385T, R504T, double (A385T/R504T) showed no significant differences current density voltage-dependent activation. Unexpectedly, rightward shift inactivation three groups mutation. Besides, recovery from faster than WT. These results suggest that, contrary expected mechanism BrS, cause gain-of-function NaV1.5. However, densities R504T with β-subunit SCN1B significantly suppressed but not different voltage dependent activation all mutants slower mutation interacting responsible pathophysiological function BrS. Funding Acknowledgement Type funding sources: None.