KTX3, the kaliotoxin from Buthus occitanus tunetanus scorpion venom: one of an extensive family of peptidyl ligands of potassium channels

A new ligand of the K+ channels sensitive to KTX was purified from the veno m of Buthus occitanus tunetanus, using two steps of high-performance-liquid -chromatography and by following its ability to compete with [I-125]-KTX fo r binding to the KTX receptor on rat brain synaptosomes. Amino-acid analysi s, amino acid sequencing and mass spectroscopy defined this new ligand, KTX 3, as a 37-amino acid peptide, with three disulfide bridges, Its sequence s hares 76% identity with KTX, The main differences between the two peptides are in the N-terminal region and the residue position 34 located in the reg ion involved in channel recognition. These differences may explain the 5-fo ld lower binding affinity of KTX3. IC50=50 pM, than KTX to rat brain synapt osomes, Specific antibodies raised against KTX (1-37) were not able to reco gnize KTX3. (C) 1999 Elsevier Science Ltd. All rights reserved.