The scorpion venom from Leiurus quinquestriatus (LQTX) alters the kinetics of tetrodotoxin (TTX)-sensitive channels such as the skeletal muscle sodium channel Nav1.4. In this study, we tested the effects of LQTX on the TTX-resistant sodium current generated by Nav1.8 channels in sensory neurons. Nav1.8 current was found to be resistant to LQTX, whereas LQTX slowed inactivation of the current generated by Nav1.4 and induced a persistent current. LQTX has been shown to bind the S3-S4 linker of domain four (D4S3-S4) of rat brain Nav1.2 sodium channels. Sequence analysis shows that the D4S3-S4 linker is longer in Nav1.8 than in Nav1.4 by four amino acids: Serine; Leucine; Glutamic acid; and Aspargine (SLEN). Nav1.4-SLEN, a chimera construct carrying SLEN at the analogous position in the D4S3-S4 linker, was also found to be resistant to LQTX. Therefore, we conclude that the tetrapeptide SLEN at the D4S3-S4 linker region is sufficient to make Nav1.8 resistant to LQTX.
- Leiurus quinquestriatus toxin
- Na1.4-Serine, leucine, glutamic acid and aspargine
- Sodium channel
ASJC Scopus subject areas