Huwentoxin-IV

Huwentoxin IV (HwTx-IV) is a neurotoxin that was originally isolated from Haplopelma schmidti (Chinese bird spider). This lethal neurotoxin acts selectively on tetrodotoxin-sensitive (TTX-S) voltage-gated sodium channels, with an IC₅₀ of 30 nM in rat DRG neurons. It preferentially inhibits neuronal voltage-gated sodium channel subtype hNa_v1.7 (SCN9A, IC₅₀ is 26 nM), rNa_v1.2 (SCN2A, IC₅₀ is 150 nM), and rNa_v1.3 (SCN3A, IC₅₀ is 338 nM), compared with muscle subtypes rNa_v1.4 (SCN4A) and hNa_v1.5 (SCN5A) (IC₅₀ is > 10 µM).Huwentoxin IV inhibits the activation of sodium channels by trapping the voltage sensor of domain II of the site 4 in the inward, closed configuration.