| 10051544 |
Lee D, Park Y, Brown TM, Adams ME: Altered properties of neuronal sodium channels associated with genetic resistance to pyrethroids. Mol Pharmacol. 1999 Mar;55(3):584-93.
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. |
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