PT - JOURNAL ARTICLE AU - Daewoo Lee AU - Yoonseong Park AU - Thomas M. Brown AU - Michael E. Adams TI - Altered Properties of Neuronal Sodium Channels Associated with Genetic Resistance to Pyrethroids DP - 1999 Mar 01 TA - Molecular Pharmacology PG - 584--593 VI - 55 IP - 3 4099 - http://molpharm.aspetjournals.org/content/55/3/584.short 4100 - http://molpharm.aspetjournals.org/content/55/3/584.full SO - Mol Pharmacol1999 Mar 01; 55 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