An inhibitor of the Kv2.1 potassium channel isolated from the venom of a Chilean tarantula

Neuron. 1995 Oct;15(4):941-9. doi: 10.1016/0896-6273(95)90184-1.


The Kv2.1 voltage-activated K+ channel, a Shab-related K+ channel isolated from rat brain, is insensitive to previously identified peptide inhibitors. We have isolated two peptides from the venom of a Chilean tarantula, G. spatulata, that inhibit the Kv2.1 K+ channel. The two peptides, hanatoxin1 (HaTx1) and hanatoxin2 (HaTx2) are unrelated in primary sequence to other K+ channel inhibitors. The activity of HaTx was verified by synthesizing it in a bacterial expression system. The concentration dependence for both the degree of inhibition at equilibrium (Kd = 42 nM) and the kinetics of inhibition (kon = 3.7 x 10(4) M-1s-1; koff = 1.3 x 10(-3) s-1), are consistent with a bimolecular reaction between HaTx and the Kv2.1 K+ channel. Shaker-related, Shaw-related, and eag K+ channels were relatively insensitive to HaTx, whereas a Shal-related K+ channel was sensitive. Regions outside the scorpion toxin binding site (S5-S6 linker) determine sensitivity to HaTx. HaTx introduces a new class of K+ channel inhibitors that will be useful probes for studying K+ channel structure and function.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • ATP-Binding Cassette Transporters*
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Binding Sites
  • Brain Chemistry
  • Carrier Proteins / genetics
  • Electrophysiology
  • Escherichia coli / genetics
  • Escherichia coli Proteins*
  • Maltose-Binding Proteins
  • Molecular Sequence Data
  • Monosaccharide Transport Proteins*
  • Peptides / chemistry
  • Peptides / genetics
  • Peptides / pharmacology*
  • Potassium Channel Blockers*
  • Potassium Channels / chemistry
  • Potassium Channels / physiology
  • Rats
  • Recombinant Fusion Proteins / pharmacology
  • Spider Venoms / chemistry*


  • ATP-Binding Cassette Transporters
  • Carrier Proteins
  • Escherichia coli Proteins
  • Maltose-Binding Proteins
  • Monosaccharide Transport Proteins
  • Peptides
  • Potassium Channel Blockers
  • Potassium Channels
  • Recombinant Fusion Proteins
  • Spider Venoms
  • hanatoxin
  • maltose transport system, E coli