Isolation of δ‐missulenatoxin‐Mb1a, the major vertebrate‐active spider δ‐toxin from the venom of Missulena bradleyi (Actinopodidae)1

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Abstract
The present study describes the isolation and pharmacological characterisation of the neurotoxin δ‐missulenatoxin‐Mb1a (δ‐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 δ‐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, δ‐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 δ‐atracotoxins (δ‐ACTX) from Australian funnel‐web spiders including conservation of all eight cysteine residues. In addition to actions on sodium channel gating and kinetics to δ‐ACTX, δ‐MSTX‐Mb1a caused significant insect toxicity at doses up to 2000 pmol/g. δ‐MSTX‐Mb1a therefore provides evidence of a highly conserved spider δ‐toxin from a phylogenetically distinct spider family that has not undergone significant modification.

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