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Modification of sodium channel gating and kinetics by versutoxin from the Australian funnel-web spiderHadronyche versuta

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Abstract

The effects of a neurotoxin (versutoxin VTX), purified from the venom of the Australian Blue Mountains funnel-web spiderHadronyche versuta, on the ionic currents in rat dorsal root ganglion cells were investigated under voltage-clamp conditions using the whole-cell patch-clamp technique. VTX had no effect on tetrodotoxin-resistant (TTX-R) sodium currents or potassium currents. In contrast VTX produced a dosedependent slowing or removal of tetrodotoxin-sensitive (TTX-S) sodium current inactivation, a reduction in peak TTX-S sodium current but did not markedly slow tail current kinetics of TTX-S sodium currents. This steady-state sodium current was maintained during prolonged depolarizations at all test potentials and the reduction in sodium current amplitude produced by VTX had an apparentK i of 37 nM. In the presence of 32 nM VTX the voltage dependence of steady-state sodium channel inactivation (h ∞) also showed a significant 7 mV shift in the voltage midpoint in the hyperpolarizing direction, with no change in the slope factor. In addition there was a steady-state or non-inactivating component present (14±2% of maximal sodium current) at prepulse potentials more depolarized than −40 mV, potentials which normally inactivate all TTX-S sodium channels. Finally, there was an observed increase in the rate of recovery from inactivation in the presence of VTX. These selective actions of VTX on sodium channel gating and kinetics are similar to those ofα-scorpion and sea anemone toxins.

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Authors and Affiliations

  1. Department of Biochemistry and Physiology, University of Technology, Sydney, Level 14 City Campus, 2007, Broadway, NSW, Australia

    Graham M. Nicholson & Max Willow

  2. Department of Biological Sciences, Deakin University, 3217, Geelong, Victoria, Australia

    Merlin E. H. Howden

  3. Department of Pharmacology, Northwestern University Medical School, 60611, Chicago, IL, USA

    Toshio Narahashi

Authors
  1. Graham M. Nicholson
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  2. Max Willow
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  3. Merlin E. H. Howden
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  4. Toshio Narahashi
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Nicholson, G.M., Willow, M., Howden, M.E.H. et al. Modification of sodium channel gating and kinetics by versutoxin from the Australian funnel-web spiderHadronyche versuta . Pflügers Arch. 428, 400–409 (1994). https://doi.org/10.1007/BF00724524

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  • DOI: https://doi.org/10.1007/BF00724524

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