Scorpion toxins interact with nicotinic acetylcholine receptors

FEBS Lett. 2019 Oct;593(19):2779-2789. doi: 10.1002/1873-3468.13530. Epub 2019 Jul 18.

Abstract

Neurotoxins are among the main components of scorpion and snake venoms. Scorpion neurotoxins affect voltage-gated ion channels, while most snake neurotoxins target ligand-gated ion channels, mainly nicotinic acetylcholine receptors (nAChRs). We report that scorpion venoms inhibit α-bungarotoxin binding to both muscle-type nAChR from Torpedo californica and neuronal human α7 nAChR. Toxins inhibiting nAChRs were identified as OSK-1 (α-KTx family) from Orthochirus scrobiculosus and HelaTx1 (κ-KTx family) from Heterometrus laoticus, both being blockers of voltage-gated potassium channels. With an IC50 of 1.6 μm, OSK1 inhibits acetylcholine-induced current through mouse muscle-type nAChR heterologously expressed in Xenopus oocytes. Other well-characterized scorpion toxins from these families also bind to Torpedo nAChR with micromolar affinities. Our results indicate that scorpion neurotoxins present target promiscuity.

Keywords: neurotoxin; nicotinic acetylcholine receptor; potassium channels; scorpion; snake; venom.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Mice
  • Nicotinic Antagonists / chemistry
  • Nicotinic Antagonists / classification
  • Nicotinic Antagonists / pharmacology*
  • Protein Binding
  • Receptors, Nicotinic / chemistry
  • Receptors, Nicotinic / metabolism*
  • Scorpion Venoms / chemistry
  • Scorpion Venoms / classification
  • Scorpion Venoms / pharmacology*
  • Xenopus

Substances

  • Nicotinic Antagonists
  • Receptors, Nicotinic
  • Scorpion Venoms