Elucidation of pyrethroid and DDT receptor sites in the voltage-gated sodium channel.

Journal Article (Review;Journal Article)

DDT and pyrethroid insecticides were among the earliest neurotoxins identified to act on voltage-gated sodium channels. In the 1960s, equipped with, at the time, new voltage-clamp techniques, Professor Narahashi and associates provided the initial evidence that DDT and allethrin (the first commercial pyrethroid insecticide) caused prolonged flow of sodium currents in lobster and squid giant axons. Over the next several decades, continued efforts by Prof. Narahashi's group as well as other laboratories led to a comprehensive understanding of the mechanism of action of DDT and pyrethroids on sodium channels. Fast forward to the 1990s, genetic, pharmacological and toxicological data all further confirmed voltage-gated sodium channels as the primary targets of DDT and pyrethroid insecticides. Modifications of the gating kinetics of sodium channels by these insecticides result in repetitive firing and/or membrane depolarization in the nervous system. This mini-review focuses on studies from Prof. Narahashi's pioneer work and more recent mutational and computational modeling analyses which collectively elucidated the elusive pyrethroid receptor sites as well as the molecular basis of differential sensitivities of insect and mammalian sodium channels to pyrethroids.

Full Text

Duke Authors

Cited Authors

  • Zhorov, BS; Dong, K

Published Date

  • May 2017

Published In

Volume / Issue

  • 60 /

Start / End Page

  • 171 - 177

PubMed ID

  • 27567732

Pubmed Central ID

  • PMC5730328

Electronic International Standard Serial Number (EISSN)

  • 1872-9711

International Standard Serial Number (ISSN)

  • 0161-813X

Digital Object Identifier (DOI)

  • 10.1016/j.neuro.2016.08.013

Language

  • eng