ELUCIDATING THE DIFFERENTIAL IMPACTS OF EQUIVALENT GATING-CHARGE MUTATIONS IN VOLTAGE-GATED SODIUM CHANNELS.

ABSTRACT: Voltage-gated sodium (Na_v) channels are pivotal for cellular signaling and mutations in Na_v channels can lead to excitability disorders in cardiac, muscular, and neural tissues. A major cluster of pathological mutations localizes in the voltage-sensing domains (VSDs), resulting in either gain-of-function (GoF), loss-of-function (LoF) effects, or both. However, the mechanism behind this functional divergence of mutations at equivalent positions remains elusive. Through hotspot analysis, we identified three gating charges (R1, R2, and R3) as major mutational hotspots in VSDs. The same amino-acid substitutions at equivalent gating-charge positions in VSD_I and VSD_II of the cardiac sodium channel Na_v1.5 show differential gating-property imp

SUBMITTER: Elhanafy E 

PROVIDER: S-EPMC11419121 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature