Isolation of delta-missulenatoxin-Mb1a, the major vertebrate-active spider delta-toxin from the venom of Missulena bradleyi (Actinopodidae)

Elsevier Science Bv
Publication Type:
Journal Article
Febs Letters, 2003, 554 (1-2), pp. 211 - 218
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The present study describes the isolation and pharmacological characterisation of the neurotoxin ?-missulenatoxin-Mb1a (?-MSTX-Mb1a) from the venom of the male Australian eastern mouse spider, Missulena bradleyi. This toxin was isolated using reverse-phase high-performance liquid chromatography and was subsequently shown to cause an increase in resting tension, muscle fasciculation and a decrease in indirect twitch tension in a chick biventer cervicis nerve-muscle bioassay. Interestingly, these effects were neutralised by antivenom raised against the venom of the Sydney funnel-web spider Atrax robustus. Subsequent whole-cell patch-clamp electrophysiology on rat dorsal root ganglion neurones revealed that ?-MSTX-Mb1a caused a reduction in peak tetrodotoxin (TTX)-sensitive sodium current, a slowing of sodium current inactivation and a hyperpolarising shift in the voltage at half-maximal activation. In addition, ?-MSTX-Mb1a failed to affect TTX-resistant sodium currents. Subsequent Edman degradation revealed a 42-residue peptide with unusual N- and C-terminal cysteines and a cysteine triplet (Cys14-16). This toxin was highly homologous to a family of ?-atracotoxins (?-ACTX) from Australian funnel-web spiders including conservation of all eight cysteine residues. In addition to actions on sodium channel gating and kinetics to ?-ACTX, ?-MSTX-Mb1a caused significant insect toxicity at doses up to 2000 pmol/g. ?-MSTX-Mb1a therefore provides evidence of a highly conserved spider ?-toxin from a phylogenetically distinct spider family that has not undergone significant modification.
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