Purification, characterization, and synthesis of three novel toxins from the Chinese scorpion Buthus martensi, which act on K+ channels

Biochemistry. 1997 Nov 4;36(44):13473-82. doi: 10.1021/bi971044w.


Three novel toxins belonging to the scorpion K+ channel-inhibitor family were purified to homogeneity from the venom of the Chinese scorpion Buthus martensi. They have been identified according to their molecular mass (3800-4300 Da) and their neurotoxicity in mice and characterized as 37-amino acid peptides. One of them shows 81-87% sequence identity with members of the kaliotoxin group (named BmKTX), whereas the other two, named BmTX1 and BmTX2, show 65-70% identity with toxins of the charybdotoxin group. Their chemical synthesis by the Fmoc methodology allowed us to show that BmKTX, unlike BmTX1 and BmTX2, possesses an amidated C-terminal extremity. Toxicity assays in vivo established that they are lethal neurotoxic agents in mice (LD50s of 40-95 ng per mouse). Those toxins proved to be potent inhibitors of the voltage-gated K+ channels, as they were able to compete with [125I]kaliotoxin for its binding to rat brain synaptosomes (IC50s of 0.05-1 nM) and to block the cloned voltage-gated K+ channel Kv1.3 from rat brain, expressed in Xenopus oocytes (IC50s of 0.6-1.6 nM). BmTX1 and BmTX2 were also shown to compete with [125I]charybdotoxin for its binding to the high-conductance Ca2+-activated K+ channels present on bovine aorta sarcolemmal membranes (IC50s of 0.3-0.6 nM). These new sequences show multipoint mutations when compared to the other related scorpion K+ channel toxins and should prove to be useful probes for studying the diverse family of K+ channels.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Aorta
  • Binding, Competitive
  • Cattle
  • Charybdotoxin / chemistry
  • Chemical Phenomena
  • Chemistry, Physical
  • Intracellular Membranes / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Neurotoxins / chemistry*
  • Potassium Channels / drug effects*
  • Potassium Channels / metabolism
  • Rats
  • Sarcolemma / drug effects
  • Scorpion Venoms / chemical synthesis
  • Scorpion Venoms / isolation & purification*
  • Scorpion Venoms / toxicity*


  • KTX toxin, Buthus
  • Neurotoxins
  • Potassium Channels
  • Scorpion Venoms
  • TX1 toxin, Buthus
  • TX2 toxin, Buthus
  • Charybdotoxin