The pharmacological flexibility of the insect voltage gated sodium channel: toxicity of AaIT to knockdown resistant (kdr) flies

AaIT is an insect selective neurotoxic polypeptide shown to affect insect n euronal sodium conductance by binding to excitable sodium channels. In the present study the paralytic potency of AaIT to wild type and various mutant strains of houseflies (Musca domestica) and fruitflies (Drosophila melanog aster) was examined and it has been shown that: On the basis of body weight when compared to published data on Sarcophaga f alculata blowflies, the Musca and Drosophila flies reveal at least two orde rs of magnitude decreased susceptibility to the AaIT. When compared to wild type flies the toxicity of AaIT is greatly altered in knockdown resistant fly strains which are mutated in their pam gene encodi ng the voltage gated sodium channel. Several strains, with genetically mapped para mutations conferring pyrethro id resistance, exhibited opposing response to AaIT. The para ts2 Drosophila strain, with a point of mutation in domain I of the para gene conferring a 6-fold resistance to deltamethrin also showed about 15-fold tolerance to A aIT. On the other hand the Musca kdr and super-kdr flies, with a single or a double point mutation, respectively in domain II of the para gene, are ab out 9- and 14-fold more susceptible to AaTT, respectively. The above data are interpreted in terms of the pharmacological diversity an d flexibility ("allosteric coupling") of voltage fated sodium channels and their implications for the management of pesticide resistance are discussed . (C) 1999 Elsevier Science Ltd. All rights reserved.