A number of peptide toxins from funnel web spiders are known to be selectively toxic to insects. One of these, ω-hexatoxin-Hv1a (previously ω-atracotoxin-Hv1a), has long been thought to primarily act as a blocker of insect voltage activated calcium channels. By radio-labelling the toxin and characterizing its binding to insect neuronal membranes, we show that this toxin binds with low nM affinity to a sub-set of the family of insect nicotinic acetylcholine receptors, and further that it acts as a positive allosteric modulator of agonist binding. These effects are more potent than those reported for action at calcium channels and more consistent with the toxin's neuroexcitatory toxicology. The structure activity relationship for this effect also correlates well with that for insecticidal activity and so it is likely that action at the nicotinic receptor is what leads to the insecticidal effect. The presentation will detail the studies that led to this conclusion and also show how this and other spider toxins interact with insecticides known to act at both orthosteric and allosteric sites of the nicotinic acetylcholine receptor.

Spider toxins as novel allosteric modulators of insect nicotinic receptors

2019 Fall National Meeting

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