A novel conotoxin from Conus betulinus, kappa-BtX, unique in cysteine pattern and in function as a specific BK channel modulator

J Biol Chem. 2003 Apr 11;278(15):12624-33. doi: 10.1074/jbc.M210200200. Epub 2003 Jan 23.


A novel conotoxin, kappa-conotoxin (kappa-BtX), has been purified and characterized from the venom of a worm-hunting cone snail, Conus betulinus. The toxin, with four disulfide bonds, shares no sequence homology with any other conotoxins. Based on a partial amino acid sequence, its cDNA was cloned and sequenced. The deduced sequence consists of a 26-residue putative signal peptide, a 31-residue mature toxin, and a 13-residue extra peptide at the C terminus. The extra peptide is cleaved off by proteinase post-processing. All three Glu residues are gamma-carboxylated, one of the two Pro residues is hydroxylated at position 27, and its C-terminal residue is Pro-amidated. The monoisotopic mass of the toxin is 3569.0 Da. Electrophysiological experiments show that: 1) among voltage-gated channels, kappa-BtX is a specific modulator of K(+) channels; 2) among the K channels, kappa-BtX specifically up-modulates the Ca(2+)- and voltage-sensitive BK channels (252 +/- 47%); 3) its EC(50) is 0.7 nm with a single binding site (Hill = 0.88); 4) the time constant of wash-out is 8.3 s; and 5) kappa-BtX has no effect on single channel conductance, but increases the open probability of BK channels. It is concluded that kappa-BtX is a novel specific biotoxin against BK channels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Calcium Channels / physiology
  • Cells, Cultured
  • Chromaffin Cells / drug effects
  • Chromaffin Cells / physiology
  • Chromatography, Gel
  • Conotoxins / chemistry*
  • Conotoxins / isolation & purification
  • Conotoxins / pharmacology*
  • DNA Primers
  • DNA, Complementary / genetics
  • Large-Conductance Calcium-Activated Potassium Channels
  • Molecular Sequence Data
  • Mollusca
  • Potassium Channels / physiology
  • Potassium Channels, Calcium-Activated / antagonists & inhibitors*
  • Rats
  • Rats, Wistar
  • Sodium Channels / physiology
  • Spectrometry, Mass, Electrospray Ionization
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization


  • Calcium Channels
  • Conotoxins
  • DNA Primers
  • DNA, Complementary
  • Large-Conductance Calcium-Activated Potassium Channels
  • Potassium Channels
  • Potassium Channels, Calcium-Activated
  • Sodium Channels
  • kappa-conotoxin BtX

Associated data

  • GENBANK/AF208661