Spliced isoforms of the cardiac Nav1.5 channel modify channel activation by distinct structural mechanisms.

ABSTRACT: Alternative splicing is an important cellular mechanism that fine tunes the gating properties of both voltage- and ligand-gated ion-channels. The cardiac voltage-gated sodium channel, Nav1.5, is subject to alternative splicing of the DI S3-S4 linker, which generates two types of channels with different activation properties. Here, we show that the gating differences between the adult (mH1) and neonatal (Nav1.5e) isoforms of Nav1.5 are mediated by two amino acid residues: Thr/Ser at position 207 and Asp/Lys at position 211. Electrophysiological experiments, in conjunction with molecular dynamics simulations, revealed that each residue contributes equally to the overall gating shifts in activation, but that the underlying structural mechanisms are different. Asp/Lys at position 211 acts thro

SUBMITTER: Mancino AS 

PROVIDER: S-EPMC8939363 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature