Structure and function of Buthus eupeus scorpion neurotoxins

At present the investigation of the complex mechanism of the signal conductance between nerve cells and their target organ is closely connected with application of neurotoxins as a valuable tool for study of important sites involved in nerve transmission. Particular interest is attributed to neurotoxins from scorpion venoms which slow down the inactivation rate of fast sodium channels of the excitable membrane. Fifteen different toxins have been isolated from Buthus eupeus scorpion venom by means of the combination of gel and ion exchange chromatography. The homologous insectotoxins I₁, I₃, I₄, and I₅ belong to the new structural type of scorpion toxins. The essential features of these toxins are low molecular weight (ca. 4000) and the presence of two or three methionine residues in their amino acid compositions. The complete amino acid sequences of two insectotoxins and one mammalian toxin have been estimated. All mammalian neurotoxins in concentration from 10^?9M to 10^?7M slow down the inactivation rate of fast sodium channels. The direct covalent binding of photosensitive radioactive neurotoxin derivatives presents one of the most effective approaches to the localization of the functionally important components of the fast sodium channels. Thus far 2,4-dinitro-5-fluorophenylazide has been used for chemical modification of the mammalian neurotoxin M₁₀. The prepared monosubstituted photosensitive neurotoxin derivative possessed a high biological activity according to the voltage clamp data. The neurotoxin derivative has been iodinated by ¹²⁵I, the resulted product being both radioactively and photoaffinity labeled. Both native neurotoxin M₁₀ and sea anemone toxin competitively inhibit the reception of the scorpion toxin derivative by rat brain synaptosomes. It was shown that covalent toxin-receptor complexes are composed of two protein components with molecular weights 76,000 and 51,000, being near equal for synaptosomes, neuroblastoma cells, and crab nerve plasma membranes.