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Background
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Huwentoxin 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 hNav1.7 (SCN9A) (IC50 is 26 nM), rNav1.2 (SCN2A) (IC50 is 150 nM), and rNav1.3 (SCN3A) (IC50 is 338 nM), compared with muscle subtypes rNav1.4 (SCN4A) and hNav1.5 (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.
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