TY - JOUR T1 - Altered Properties of Neuronal Sodium Channels Associated with Genetic Resistance to Pyrethroids JF - Molecular Pharmacology JO - Mol Pharmacol SP - 584 LP - 593 VL - 55 IS - 3 AU - Daewoo Lee AU - Yoonseong Park AU - Thomas M. Brown AU - Michael E. Adams Y1 - 1999/03/01 UR - http://molpharm.aspetjournals.org/content/55/3/584.abstract N2 - 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 ER -