A single amino acid change makes a rat neuronal sodium channel highly sensitive to pyrethroid insecticides.
Two amino acid substitutions in a housefly sodium channel, L1014F in domain IIS6 and M918T in the IIS4-S5 linker, have been identified in kdr and super-kdr pyrethroid-resistant phenotypes, respectively. Unlike their native insect counterparts, mammalian sodium channels are only weakly sensitive to pyrethroids. Do the sodium channels of mammal and pyrethroid-resistant housefly share similar structural characteristics that account for their low pyrethroid sensitivities? We report here that substitution of isoleucine for methionine at position 874 (equivalent to the super-kdr site 918 in the housefly) in the rat IIA alpha-subunit causes a 100-fold increase in sensitivity.
Vais
H
H
Molecular Toxicology Group, School of Biological Sciences, University of Nottingham, University Park, Nottingham, UK.
Atkinson
S
S
Eldursi
N
N
Devonshire
A L
AL
Williamson
M S
MS
Usherwood
P N
PN
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics*; D000818:Animals; D001921:Brain; D004351:Drug Resistance / Q000235:genetics; D004553:Electric Conductivity; D007306:Insecticides / Q000378:metabolism / Q000494:pharmacology*; D007532:Isoleucine / Q000235:genetics; D008969:Molecular Sequence Data; D009570:Nitriles; D009865:Oocytes; D010641:Phenotype; D011722:Pyrethrins / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D016415:Sequence Alignment; D026941:Sodium Channel Blockers; D015222:Sodium Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis
D007306:Insecticides; D009570:Nitriles; D011722:Pyrethrins; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D007532:Isoleucine; C017180:decamethrin