title: Sensitivity of the Drosophila para sodium channel to DDT is not lowered by the super-kdr mutation M918T on the IIS4-S5 linker that profoundly reduces sensitivity to permethrin and deltamethrin.
abstract: DDT inhibits Na channel inactivation and deactivation, promotes Na channel activation and reduces the resting potential of Xenopus oocytes expressing the Drosophila para Na channel. These changes are only marginally influenced by the single mutation M918T (super-kdr) but are reduced approximately 10-fold by either the single mutation L1014F (kdr) or the double mutation L1014F+M918T, both of which confer resistance to the pyrethroids permethrin and deltamethrin. We conclude that DDT binds either to or in the region of L1014 on IIS6 but only weakly to M918 on the IIS4-S5 linker, which is part of a high-affinity binding site for permethrin and deltamethrin.
authors.affiliation: School of Biology, The University of Nottingham, Nottingham, NG7 2RD, UK. peter.usherwood@nottingham.ac.uk
authors.forename: P N R
authors.initials: PN
authors.lastname: Usherwood
authors.forename: H
authors.initials: H
authors.lastname: Vais
authors.forename: B P S
authors.initials: BP
authors.lastname: Khambay
authors.forename: T G E
authors.initials: TG
authors.lastname: Davies
authors.forename: M S
authors.initials: MS
authors.lastname: Williamson
mesh_terms: D000818:Animals; D003634:DDT; D029721:Drosophila Proteins / Q000187:drug effects* / Q000235:genetics*; D004331:Drosophila melanogaster / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007305:Insecticide Resistance / Q000235:genetics; D007306:Insecticides; D015640:Ion Channel Gating / Q000187:drug effects / Q000235:genetics; D007532:Isoleucine / Q000235:genetics; D008564:Membrane Potentials / Q000187:drug effects; D009570:Nitriles; D026023:Permethrin; D017354:Point Mutation; D011722:Pyrethrins; D015222:Sodium Channels / Q000187:drug effects* / Q000235:genetics*; D014982:Xenopus laevis
chemical_list: D029721:Drosophila Proteins; D004791:Enzyme Inhibitors; D007306:Insecticides; D009570:Nitriles; D011722:Pyrethrins; D015222:Sodium Channels; C469950:para protein, Drosophila; D007532:Isoleucine; C017180:decamethrin; D026023:Permethrin; D003634:DDT