Altered properties of neuronal sodium channels associated with genetic resistance to pyrethroids.
Genetic resistance to pyrethroid insecticides involves nervous system insensitivity linked to regulatory and structural genes of voltage-sensitive sodium channels. We examined the properties and relative density of sodium channels in central neurons of susceptible and pyrethroid-resistant (Pyr-R) insects that were homozygous for the amino acid substitution V421M in the I-S6 transmembrane segment. Pyr-R sodium channels show approximately 21-fold lower sensitivity to the synthetic pyrethroid permethrin and a approximately 2-fold increased sensitivity to the alpha-scorpion toxin LqhalphaIT. Pyr-R channels also exhibit altered gating properties, including a approximately 13 mV positive shift in voltage-dependent activation and approximately 7 mV positive shift in steady-state inactivation. Consistent with these changes in gating behavior, Pyr-R central neurons are less excitable, as evidenced by an approximately 11 mV elevation of action potential threshold. No differences in sodium channel density are evident. The altered properties of Pyr-R sodium channels provide a plausible molecular basis for nervous system insensitivity associated with pyrethroid resistance.
Lee
D
D
Department of Entomology and Neuroscience, University of California, Riverside 92521, USA.
Park
Y
Y
Brown
T M
TM
Adams
M E
ME
D000818:Animals; D007305:Insecticide Resistance / Q000235:genetics; D007306:Insecticides / Q000494:pharmacology*; D007700:Kinetics; D007915:Lepidoptera; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D026023:Permethrin; D017354:Point Mutation; D011722:Pyrethrins / Q000494:pharmacology*; D012604:Scorpion Venoms / Q000494:pharmacology; D015222:Sodium Channels / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology
D007306:Insecticides; D011722:Pyrethrins; D012604:Scorpion Venoms; D015222:Sodium Channels; D013779:Tetrodotoxin; D026023:Permethrin