RT Journal Article SR Electronic T1 Altered Properties of Neuronal Sodium Channels Associated with Genetic Resistance to Pyrethroids JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 584 OP 593 VO 55 IS 3 A1 Daewoo Lee A1 Yoonseong Park A1 Thomas M. Brown A1 Michael E. Adams YR 1999 UL http://molpharm.aspetjournals.org/content/55/3/584.abstract AB 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 ∼21-fold lower sensitivity to the synthetic pyrethroid permethrin and a ∼2-fold increased sensitivity to the α-scorpion toxin LqhαIT. Pyr-R channels also exhibit altered gating properties, including a ∼13 mV positive shift in voltage-dependent activation and ∼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 ∼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. The American Society for Pharmacology and Experimental Therapeutics