Voltage‐Gated Sodium Channels as Insecticide Targets

Dong, Ke

doi:10.1002/3527602038.ch14

Cited by 5 publications

(5 citation statements)

References 28 publications

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“…Substitutions of the leucine residue in IIS6 (corresponding to Leu993 in BgNa v ) have been found in diverse insect species and seem to be the most common type of naturally occurring kdr mutations in insects (Dong, 2002;Soderlund and Knipple, 2003). We showed that the L993F mutation, like the F1519I mutation, reduced pyrethroid binding to the cockroach sodium channel.…”

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confidence: 80%

Identification of Amino Acid Residues in the Insect Sodium Channel Critical for Pyrethroid Binding

Tan

Liu

Wang

et al. 2005

Molecular Pharmacology

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The voltage-gated sodium channel is the primary target site of pyrethroids, which constitute a major class of insecticides used worldwide. Pyrethroids prolong the opening of sodium channels by inhibiting deactivation and inactivation. Despite numerous attempts to characterize pyrethroid binding to sodium channels in the past several decades, the molecular determinants of the pyrethroid binding site on the sodium channel remain elusive. Here, we show that an F-to-I substitution at 1519 (F1519I) in segment 6 of domain III (IIIS6) abolished the sensitivity of the cockroach sodium channel expressed in Xenopus laevis oocytes to all eight structurally diverse pyrethroids examined, including permethrin and deltamethrin. In contrast, substitution by tyrosine or tryptophan reduced the channel sensitivity to deltamethrin only by 3-to 10-fold, indicating that an aromatic residue at this position is critical for the interaction of pyrethroids with sodium channels. The F1519I mutation, however, did not alter the action of two other classes of sodium channel toxins, batrachotoxin (a site 2 toxin) and Lqh␣-IT (a site 3 toxin). Schild analysis using competitive interaction of pyrethroid-stereospecific isomers demonstrated that the F1519W mutation and a previously known pyrethroid-resistance mutation, L993F in IIS6, reduced the binding affinity of 1S-cispermethrin, an inactive isomer that shares the same binding site with the active isomer 1R-cis-permethrin. Our results provide the first direct proof that Leu993 and Phe1519 are part of the pyrethroid receptor site on an insect sodium channel.

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confidence: 80%

Identification of Amino Acid Residues in the Insect Sodium Channel Critical for Pyrethroid Binding

Tan

Liu

Wang

et al. 2005

Molecular Pharmacology

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129

135

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“…The voltage‐gated sodium channel (VGSC) is the target of pyrethroids. Pyrethroids are known to exert their insecticidal effects by altering the function of voltage‐sensitive sodium channels in nerve membranes 14–18. Knockdown resistance ( kdr ) is the reduction in the sensitivity of the insect nervous system to pyrethroids, mainly caused by gene mutations in the sodium channel.…”

Section: Introductionmentioning

confidence: 99%

The sodium channel gene in Tetranychus cinnabarinus (Boisduval): identification and expression analysis of a mutation associated with pyrethroid resistance

Feng

Zhao

Sun

et al. 2011

Pest Management Science

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“…Specific binding of radiolabeled pyrethroids was detected in rat brain membrane preparations (Trainer et al, 1997). However, attempts to characterize specific binding of pyrethroids to insect nerve membrane preparations have failed because of the extreme hydrophobicity of pyrethroids, resulting in extremely high nonspecific binding (Dong, 1993; Pauron et al, 1989; Rossignol, 1988). …”

Section: Distinct Site Of Action Of Pyrethroids In the Sodium Channelmentioning

confidence: 99%

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

Zhorov

Dong

2017

NeuroToxicology

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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.

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Voltage‐Gated Sodium Channels as Insecticide Targets

Cited by 5 publications

References 28 publications

Identification of Amino Acid Residues in the Insect Sodium Channel Critical for Pyrethroid Binding

Identification of Amino Acid Residues in the Insect Sodium Channel Critical for Pyrethroid Binding

The sodium channel gene in Tetranychus cinnabarinus (Boisduval): identification and expression analysis of a mutation associated with pyrethroid resistance

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

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