Batrachotoxin acts as a stent to hold open homotetrameric prokaryotic voltage-gated sodium channels.

ABSTRACT: Batrachotoxin (BTX), an alkaloid from skin secretions of dendrobatid frogs, causes paralysis and death by facilitating activation and inhibiting deactivation of eukaryotic voltage-gated sodium (Nav) channels, which underlie action potentials in nerve, muscle, and heart. A full understanding of the mechanism by which BTX modifies eukaryotic Nav gating awaits determination of high-resolution structures of functional toxin-channel complexes. Here, we investigate the action of BTX on the homotetrameric prokaryotic Nav channels NaChBac and NavSp1. By combining mutational analysis and whole-cell patch clamp with molecular and kinetic modeling, we show that BTX hinders deactivation and facilitates activation in a use-dependent fashion. Our molecular model shows the horseshoe-shaped BTX molecule b

SUBMITTER: Finol-Urdaneta RK 

PROVIDER: S-EPMC6363421 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature