Huwentoxin-IV. A Potent Blocker of Neuronal TTX Sensitive Voltage-Gated Na \+\ Channel.
Huwentoxin-IV is a 35 amino acid peptidyl toxin isolated from the tarantula Haplopelma schmidti venom and its structure represents a typicalcystine knot motif.
Huwentoxin-IV acts selectively on tetrodotoxin-sensitive (TTX-S) voltage-gated Na\+\ channels, with an IC \50\of 30 nM in rat DRG neurons.
It preferentially inhibits central neuronal voltage-gated Na\+\ channel subtypes: hNav1.7 (IC \50\of 26 nM), rNav1.2 (IC \50\ of 150 nM), and rNav1.3 (IC \50\of 338 nM), compared with muscle subtypes rNav1.4 and h Nav1.5 (IC \50\ is > 10 micro M).
Huwentoxin-IV inhibits Na\+\ channels by trapping the voltage sensor of domain II of the site 4 in the inward, closed configuration.
Ion Channel Modulators; Voltage - Gated Na\+\ Channel Blockers