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 (OsK-1) 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 neuroblastoma x glioma NG 108-15 hybrid cells (K-d = 1.4 x 10(-7) M) which are insensitive to apamin and sensitive to charybdotoxin. The effect of OsK-1 was reversible and concentration dependent.