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

FEBS Letters

Birinyi-Strachan, Liesl C.⁴  Connor, Mark¹  Nicholson, Graham M.⁴  Szeto, Tim H.²  Christie, Macdonald J.¹  Smith, Ross³  King, Glenn F.² 

[1] Department of Pharmacology, University of Sydney, Sydney, N.S.W. 2006, Australia;Department of Biochemistry, University of Connecticut Health Center, Farmington, CT 06032, USA;Department of Biochemistry, University of Queensland, Brisbane, Qld. 4072, Australia;Department of Health Sciences, University of Technology, Sydney, P.O. Box 123, Broadway, N.S.W. 2007, Australia

关键词: Funnel-web spider toxin;    δ-Atracotoxin;    Sodium channel;    Scorpion toxin;    δ-ACTX-Ar1;    δ-atracotoxin-Ar1 (formerly robustoxin) from Atrax robustus;    δ-ACTX-Hv1b;    δ-atracotoxin-Hv1a (formerly versutoxin) from Hadronyche versuta;    TTX;    tetrodotoxin;    Aah II;    anti-mammal α-toxin from the scorpion Androctonus australis hector;    LqhαIT;    α-insect toxin from the scorpion Leiurus quinquestriatus hebraeus;    TFA;    trifluoroacetic acid;    rpHPLC;    reverse-phase high performance liquid chromatography;    HEPES;    N-2-hydroxyethylpiperazine-N-2-ethanesulfonic acid;    DRG;    dorsal root ganglion;    TEA;    tetraethylammonium;    PTH;    phenylthiohydantoin;   

DOI  :  10.1016/S0014-5793(00)01339-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown