δ‐Atracotoxins from Australian funnel‐web spiders compete with scorpion α‐toxin binding on both rat brain and insect sodium channels

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Abstract
δ‐Atracotoxins are novel peptide toxins from the venom of Australian funnel‐web spiders that slow sodium current inactivation in a similar manner to scorpion α‐toxins. To analyse their interaction with known sodium channel neurotoxin receptor sites we determined their effect on scorpion toxin, batrachotoxin and saxitoxin binding. Nanomolar concentrations of δ‐atracotoxin‐Hv1 and δ‐atracotoxin‐Ar1 completely inhibited the binding of the scorpion α‐toxin AaH II to rat brain synaptosomes as well as the binding of LqhαIT, a scorpion α‐toxin highly active on insects, to cockroach neuronal membranes. Moreover, δ‐atracotoxin‐Hv1 cooperatively enhanced batrachotoxin binding to rat brain synaptosomes in an analogous fashion to scorpion α‐toxins. Thus the δ‐atracotoxins represent a new class of toxins which bind to both mammalian and insect sodium channels at sites similar to, or partially overlapping with, the receptor binding sites of scorpion α‐toxins.

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