Vol. 55, Issue 3, 584-593, March 1999

Altered Properties of Neuronal Sodium Channels Associated with Genetic Resistance to Pyrethroids

Daewoo Lee, Yoonseong Park, Thomas M. Brown, and Michael E. Adams

Departments of Entomology and Neuroscience, University of California, Riverside, California (D.L., M.E.A.); Department of Entomology, University of Arizona Tucson, Arizona (Y.P.); and Department of Entomology, Clemson University, Clemson, South Carolina (T.M.B.)

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 -scorpion toxin LqhIT. 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.