Isolation and pharmacological characterisation of δ‐atracotoxin‐Hv1b, a vertebrate‐selective sodium channel toxin

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Abstract
δ‐Atracotoxins (δ‐ACTXs) are peptide toxins isolated from the venom of Australian funnel‐web spiders that slow sodium current inactivation in a similar manner to scorpion α‐toxins. We have isolated and determined the amino acid sequence of a novel δ‐ACTX, designated δ‐ACTX‐Hv1b, from the venom of the funnel‐web spider Hadronyche versuta. This 42 residue toxin shows 67% sequence identity with δ‐ACTX‐Hv1a previously isolated from the same spider. Under whole‐cell voltage‐clamp conditions, the toxin had no effect on tetrodotoxin (TTX)‐resistant sodium currents in rat dorsal root ganglion neurones but exerted a concentration‐dependent reduction in peak TTX‐sensitive sodium current amplitude accompanied by a slowing of sodium current inactivation similar to other δ‐ACTXs. However, δ‐ACTX‐Hv1b is approximately 15–30‐fold less potent than other δ‐ACTXs and is remarkable for its complete lack of insecticidal activity. Thus, the sequence differences between δ‐ACTX‐Hv1a and ‐Hv1b provide key insights into the residues that are critical for targeting of these toxins to vertebrate and invertebrate sodium channels.

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