Structural and Functional Characterization of a Novel Scorpion Toxin that Inhibits Na_V1.8 via Interactions With the DI Voltage Sensor and DII Pore Module.

ABSTRACT: Voltage-gated sodium channel Na_V1.8 regulates transmission of pain signals to the brain. While Na_V1.8 has the potential to serve as a drug target, the molecular mechanisms that shape Na_V1.8 gating are not completely understood, particularly mechanisms that couple activation to inactivation. Interactions between toxin producing animals and their predators provide a novel approach for investigating Na_V structure-function relationships. Arizona bark scorpions produce Na⁺ channel toxins that initiate pain signaling. However, in predatory grasshopper mice, toxins inhibit Na_V1.8 currents and block pain signals. A screen of synthetic peptide toxins predicted from bark scorpion venom showed that peptide NaTx36 inhibited Na⁺

SUBMITTER: George K 

PROVIDER: S-EPMC9160825 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature