A scorpion venom neurotoxin paralytic to insects that affects sodium current inactivation: purification, primary structure, and mode of action.
A new toxin, Lqh alpha IT, 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, Lqh alpha IT was highly toxic to insects, but it differed from these toxins in two important characteristics: (a) Lqh alpha IT 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 Lqh alpha IT are different from those shared by the excitatory and depressant toxins. However, in its primary structure and its effect on excitable tissues, Lqh alpha IT strongly resembled the well-characterized alpha scorpion toxins, which affect mammals. The amino acid sequence was identical with alpha toxin sequences in 55%-75% of positions. This degree of similarity is comparable to that seen among the alpha toxins themselves. Voltage- and current-clamp studies showed that Lqh alpha IT 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 Lqh alpha IT is an alpha toxin which acts on insect sodium channels.(ABSTRACT TRUNCATED AT 250 WORDS)
Eitan
M
M
Department of Zoology, Hebrew University, Jerusalem, Israel.
Fowler
E
E
Herrmann
R
R
Duval
A
A
Pelhate
M
M
Zlotkin
E
E
D000595:Amino Acid Sequence; D000818:Animals; D007313:Insecta / Q000187:drug effects / Q000378:metabolism; D007457:Iodine Radioisotopes; D007814:Larva / Q000187:drug effects; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000187:drug effects; D009498:Neurotoxins / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D012604:Scorpion Venoms / Q000032:analysis / Q000302:isolation & purification / Q000494:pharmacology / Q000633:toxicity; D012964:Sodium / Q000378:metabolism*; D010738:Type C Phospholipases / Q000302:isolation & purification / Q000494:pharmacology / Q000633:toxicity
D007457:Iodine Radioisotopes; C065190:LqhalphaIT toxin; D009498:Neurotoxins; D012604:Scorpion Venoms; D012964:Sodium; D010738:Type C Phospholipases