Point mutations in domain III of a Drosophila neuronal Na channel confer resistance to allethrin

R. L. Martin, B. Pittendrigh, J. Liu, R. Reenan, R. Ffrench-Constant, D. A. Hanck

Research output: Contribution to journalArticlepeer-review

Abstract

Voltage-gated sodium channels are the presumed site of action of pyrethroid insecticides and DDT. We screened several mutant sodium channel Drosophila lines for resistance to type I pyrethroids. In insecticidal bioassays the para74 and para(DN7) fly lines showed greater than 4-fold resistance to allethrin relative to the allethrin sensitive Canton-S control line. The amino acid substitutions of both mutants are in domain III. The point mutation associated with para74 lies within the S6 transmembrane region and the amino acid substitution associated with para(DN7) lies within the S4-S5 linker region. These sites are analogous to the mutations in domain II underlying knockdown resistance (kdr) and super-kdr, naturally occurring forms of pyrethroid resistance found in houseflies and other insects. Electrophysiological studies were performed on isolated Drosophila neurons from wild type and para74 embryos placed in primary culture for three days to two weeks. The mutant para74 sodium currents were kinetically similar to wild type currents, in activation, inactivation and time to peak. The only observed difference between para74 and wild-type neurons was in the affinity of the type I pyrethroid, allethrin. Application of 500 nM allethrin caused removal of inactivation and prolonged tail currents in wild type sodium channels but had little or no effect on para74 mutant sodium channels. (C) 2000 Elsevier Science Ltd.

Original languageEnglish (US)
Pages (from-to)1051-1059
Number of pages9
JournalInsect Biochemistry and Molecular Biology
Volume30
Issue number11
DOIs
StatePublished - Oct 19 2000

Keywords

  • Allethrin
  • Drosophila
  • Electrophysiology
  • Para mutants
  • Sodium channel

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Insect Science

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