A membrane-access mechanism of ion channel inhibition by voltage sensor toxins from spider venom

Nature. 2004 Jul 8;430(6996):232-5. doi: 10.1038/nature02632.


Venomous animals produce small protein toxins that inhibit ion channels with high affinity. In several well-studied cases the inhibitory proteins are water-soluble and bind at a channel's aqueous-exposed extracellular surface. Here we show that a voltage-sensor toxin (VSTX1) from the Chilean Rose Tarantula (Grammostola spatulata) reaches its target by partitioning into the lipid membrane. Lipid membrane partitioning serves two purposes: to localize the toxin in the membrane where the voltage sensor resides and to exploit the free energy of partitioning to achieve apparent high-affinity inhibition. VSTX1, small hydrophobic poisons and anaesthetic molecules reveal a common theme of voltage sensor inhibition through lipid membrane access. The apparent requirement for such access is consistent with the recent proposal that the sensor in voltage-dependent K+ channels is located at the membrane-protein interface.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Membrane / chemistry
  • Cell Membrane / drug effects*
  • Cell Membrane / metabolism*
  • Chromatography, High Pressure Liquid
  • Electrophysiology
  • Fluorescence
  • Ion Channel Gating / drug effects*
  • Membrane Lipids / metabolism
  • Models, Biological
  • Molecular Sequence Data
  • Peptides / chemistry*
  • Peptides / metabolism
  • Peptides / pharmacology*
  • Potassium Channels, Voltage-Gated / metabolism*
  • Spider Venoms / chemistry*
  • Spider Venoms / metabolism
  • Spider Venoms / pharmacology*
  • Tryptophan


  • Membrane Lipids
  • Peptides
  • Potassium Channels, Voltage-Gated
  • Spider Venoms
  • VSTX1 protein, Grammostola spatulata
  • Tryptophan