Structure and function of the potassium channel inhibitor from black scorpion venom

A novel inhibitor of K+ channels has been purified from the venom of the Central Asian scorpion Orthochirus scrobiculosus. For this polypeptide toxin (OsK1) with molecular mass 4205.7 Da complete amino acid sequence was determined by Edman degradation and C-terminal amino acid analysis, and was confirmed by cloning and sequencing of the toxin cDNA. OsK-1 consists of 38 amino acid residues and possesses high sequence homology with agiotoxin, kaliotoxin and some homology with other known K+-channel blockers from different scorpion venoms. The toxin was shown to block small-conductance Ca++-activated K+-channels in neuroblastomaxglioma N G 10815 hybrid cells (Kd =1.4 x M) which are insensitive to apamin and sensitive to charybdotoxin. The effect of OsK1 was reversible and concentration dependent.