A SCORPION-VENOM NEUROTOXIN PARALYTIC TO INSECTS THAT AFFECTS SODIUM CURRENT INACTIVATION - PURIFICATION, PRIMARY STRUCTURE, AND MODE OF ACTION

A new toxin, LqhαIT, which caused a unique mode of paralysis of blowfly larvae, was purified from the venom of the scorpion Leiurus quinquestriatus hebraeus, and its structural and pharmacological properties were compared to those of three other groups of neurotoxins found in Buthinae scorpion venoms. Like the excitatory and depressant insect-selective neurotoxins, LqhaIT was highly toxic to insects, but it differed from these toxins in two important characteristics: (a) LqhaIT lacked strict selectivity for insects; it was highly toxic to crustaceans and had a measurable but low toxicity to mice, (b) It did not displace an excitatory insect toxin, 125I-AaIT, from its binding sites in the insect neuronal membrane; this indicates that the binding sites for LqhaIT are different from those shared by the excitatory and depressant toxins. However, in its primary structure and its effect on excitable tissues, LqhaIT strongly resembled the well-characterized a scorpion toxins, which affect mammals. The amino acid sequence was identical with a toxin sequences in 55%-75% of positions. This degree of similarity is comparable to that seen among the α toxins themselves. Voltage- and current-clamp studies showed that LqhaIT caused an extreme prolongation of the action potential in both cockroach giant axon and rat skeletal muscle preparations as a result of the slowing and incomplete inactivation of the sodium currents. These observations indicate that LqhalT is an α toxin which acts on insect sodium channels. It should be useful as a pharmacological tool for the study of sodium channels related to insect neuronal excitability and as a model for the clarification of the structural basis for animal group specificity of neurotoxins. © 1990, American Chemical Society. All rights reserved.