Mapping the receptor site for ergtoxin, a specific blocker of ERG channels

FEBS Lett. 2002 Jan 2;510(1-2):45-9. doi: 10.1016/s0014-5793(01)03218-5.

Abstract

We show here that ergtoxin (ErgTx) is a bona fide, specific blocker of the human ether-a-go-go-related gene (HERG) channels. It does not affect the function of either M-eag or M-elk channels. A chimeric construction containing a segment of the P-region of M-eag channel inserted into the HERG channel drastically diminished or completely abolished the inhibitory effect of ErgTx, whereas chimeras of the P-region of HERG channel into M-eag channels recovered the inhibitory effect. From the P-region point mutants of HERG channel assays, only the mutant N598Q shows about 25% decrement of the ErgTx inhibitory effect. ErgTx recognizes the P-region of HERG channels, blocking the channel function with a K(d) in the order of 12 nM.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Cation Transport Proteins*
  • Chromosome Mapping
  • DNA-Binding Proteins*
  • ERG1 Potassium Channel
  • Electrophysiology
  • Ether-A-Go-Go Potassium Channels
  • Female
  • Gene Expression
  • Humans
  • Ligands
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Oocytes
  • Potassium Channel Blockers / metabolism*
  • Potassium Channel Blockers / pharmacology
  • Potassium Channels / genetics
  • Potassium Channels / metabolism*
  • Potassium Channels / physiology
  • Potassium Channels, Voltage-Gated*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Recombinant Fusion Proteins / physiology
  • Scorpion Venoms / metabolism*
  • Scorpion Venoms / pharmacology
  • Trans-Activators*
  • Transcriptional Regulator ERG
  • Xenopus laevis

Substances

  • Cation Transport Proteins
  • DNA-Binding Proteins
  • ERG protein, human
  • ERG1 Potassium Channel
  • Ether-A-Go-Go Potassium Channels
  • KCNH2 protein, human
  • KCNH6 protein, human
  • Kcnh1 protein, mouse
  • Kcnh2 protein, mouse
  • Ligands
  • Potassium Channel Blockers
  • Potassium Channels
  • Potassium Channels, Voltage-Gated
  • Recombinant Fusion Proteins
  • Scorpion Venoms
  • Trans-Activators
  • Transcriptional Regulator ERG
  • ergotoxin, Centruroides noxius