Overview
- Xiao, Y. et al. (2008) J. Biol. Chem. 283, 27300.
Alomone Labs mHuwentoxin-IV inhibits NaV1.7 currents in stably transfected HEK cells.A. Time course of mHuwentoxin-IV (#STH-101) action on NaV1.7 currents. Maximum current amplitudes were plotted as a function of time. Membrane potential was held at –100 mV and cells were stimulated by a 50 ms voltage ramp to +20 mV. 100 nM mHuwentoxin-IV were perfused as indicated by the bar (green) during 4 min. B. Superimposed examples of NaV1.7 channel current in the absence (control) and presence (green) of 100 nM mHuwentoxin-IV (taken from the experiment in A).
Huwentoxin-IV (HWTX-IV), a tetrodotoxin-sensitive (TTX-s) Na+ channel blocker, isolated from the venom of the Chinese Bird spider Ornithoctonus huwena1. A naturally modified HWTX-IV (mHWTX-IV), having a molecular mass 18 Da. lower than HWTX-IV, has also been isolated from the venom of the same spider. mHWTX-IV has been shown to have the same amino acid sequence as that of HWTX-IV, except that the N-terminal glutamic acid is replaced by pyroglutamic acid. mHWTX-IV inhibits tetrodotoxin-sensitive NaV channels of dorsal root ganglion neurons with an IC50 nearly equal to native HWTX-IV (IC50 value of 28 nM versus 26 nM). mHWTX-IV shows the same activation and inactivation kinetics seen for native HWTX-IV2.
Huwentoxin-IV preferentially inhibits hNaV1.7. NaV1.7 plays a crucial role in pain transduction with familial gain of function mutations linked to several chronic pain disorders, while loss of NaV1.7 function results in congenital insensitivity to pain3.
