A novel class of peptide found in scorpion venom with neurodepressant effects in peripheral and central nervous system of the rat

A novel toxin, named Cll9, was isolated from the venom of the scorpion Centruroides limpidus limpidus Karsch. It is composed of 63 amino acid residues closely packed by four disulfide bridges. It showed no apparent effect when injected to insects, crustaceans and i.p. to mice. However, when i.c.v. injected in the rat it immediately induced sleep, suggesting that it has a neurodepressant effect. We confirmed this by showing that it has a strong antiepileptic action, as assessed with the penicillin focus model. Its effectiveness in inhibiting Na(+) permeability in (cultured) rat peripheral ganglia further supports its neurodepressant actions. However, this peptide did not affect other Na(+) channels such as those from cerebellum granular cells in culture or the rSkM1 Na(+) channels expressed in HEK293. The cDNA and genomic regions encoding this peptide were cloned and sequenced. This peptide is synthesized as a precursor of 84 amino acid residues and processed by removing 19 amino acids (signal peptide) from the amino terminal region and a couple of lysine residues from the carboxyl end. The presence of an intron of 777 bases interrupting the region encoding the signal peptide was also revealed. A comparison of its primary sequence, with more than 100 scorpion toxins known, showed that together with toxin CsE9 they constitute a new subfamily of peptides considered to be one of the most divergent groups of scorpion toxin-like peptides discovered.