The S631A mutation causes a mechanistic switch in the block of hERG channels by CnErg1

Biophys J. 2007 Sep 15;93(6):L32-4. doi: 10.1529/biophysj.107.114561. Epub 2007 Jul 13.


We have studied the interaction of CnErg1, a member of the gamma-KTX subfamily of scorpion toxins with the inactivation-deficient S631A hERG channel. In the background of this mutation, we observed a mechanistic switch from turret block, characteristic of the action of gamma-KTXs on Kv11-type channels, to pore plugging, characteristic of alpha-KTX block of Kv1-type channels. We suggest this reflects destabilization of the outer pore (turret region) of hERG allowing access of the toxin molecule to directly plug the conduction pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution
  • Animals
  • Biophysical Phenomena
  • Biophysics
  • ERG1 Potassium Channel
  • Ether-A-Go-Go Potassium Channels / antagonists & inhibitors*
  • Ether-A-Go-Go Potassium Channels / chemistry
  • Ether-A-Go-Go Potassium Channels / genetics*
  • Ether-A-Go-Go Potassium Channels / metabolism
  • Humans
  • In Vitro Techniques
  • Ion Channel Gating / drug effects
  • Membrane Potentials / drug effects
  • Mutagenesis, Site-Directed
  • Scorpion Venoms / toxicity*


  • ERG1 Potassium Channel
  • Ether-A-Go-Go Potassium Channels
  • KCNH2 protein, human
  • Scorpion Venoms
  • ergotoxin, Centruroides noxius