Invertebrate Neuroscience

, Volume 3, Issue 2–3, pp 103–116 | Cite as

A new approach to insect-pest control—combination of neurotoxins interacting with voltage sensitive sodium channels to increase selectivity and specificity

Articles from the ICINN 97 Conference Neurotoxins and Channel Blockers

Abstract

Voltage-sensitive sodium channels are responsible for the generation of electrical signals in most excitable tissues and serve as specific targets for many neurotoxins. At least seven distinct classes of neurotoxins have been designated on the basis of physiological activity and competitive binding studies. Although the characterization of the neurotoxin receptor sites was predominantly performed using vertebrate excitable preparations, insect neuronal membranes were shown to possess similar receptor sites. We have demonstrated that the two mutually competing antiinsect excitatory and depressant scorpion toxins, previously suggested to occupy the same receptor site, bind to two distinct receptors on insect sodium channels. The latter provides a new approach to their combined use in insect control strategy. Although the sodium channel receptor sites are topologically separated, there are strong allosteric interactions among them. We have shown that the lipid-soluble sodium channel activators, veratridine and brevetoxin, reveal divergent allosteric modulation on scorpion α-toxins binding at homologous receptor sites on mammalian and insect sodium channels. The differences suggest a functionally important structural distinction between these channel subtypes. The differential allosteric modulation may provide a new approach to increase selective activity of pesticides on target organisms by simultaneous application of allosterically interacting drugs, designed on the basis of the selective toxins. Thus, a comparative study of neurotoxin receptor sites on mammalian and invertebrate sodium channels may elucidate the structural features involved in the binding and activity of the various neurotoxins, and may offer new targets and approaches to the development of highly selective pesticides.

Key Words

neurotoxin sodium channel allosteric interaction scorpion toxin insect toxin 

Abbreviations of scorpion venom toxins

AaH I, II, III, IT

toxins 1-3 and insect toxin (IT) from AaH-the North African scorpionAndroctonus australis Hector

BjIT1, IT2

Bj-the Israeli black scorpionButhotus judaicus

LqhIT2, LqhαIT

Lqh-the Israeli yellow scorpionLeiurus quinquestriatus hebraeus

Lqq V, IT1, IT2

Lqq-the African scorpionLeiurus quinquestriatus quinquestriatus

Bom III, IV

Bom-the African scorpionButhus occitanus mordochei

TxVI

δ-conotoxin TxVI from the marine Cone snailConus textile

Ts VII

Ts-the Brazilian scorpionTityus serrulatus

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Copyright information

© Sheffield Academic Press 1997

Authors and Affiliations

  1. 1.Department d'Ingenierie et d'Etudes des ProteinesCEAGif-sur-YvetteFrance

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