Skip to main content
SpringerLink
Log in

Molecular mechanisms of pyrethroid insecticide neurotoxicity: recent advances

  • Review Article
  • Published:
Archives of Toxicology Aims and scope Submit manuscript

Abstract

Synthetic pyrethroid insecticides were introduced into widespread use for the control of insect pests and disease vectors more than three decades ago. In addition to their value in controlling agricultural pests, pyrethroids are at the forefront of efforts to combat malaria and other mosquito-borne diseases and are also common ingredients of household insecticide and companion animal ectoparasite control products. The abundance and variety of pyrethroid uses contribute to the risk of exposure and adverse effects in the general population. The insecticidal actions of pyrethroids depend on their ability to bind to and disrupt voltage-gated sodium channels of insect nerves. Sodium channels are also important targets for the neurotoxic effects of pyrethroids in mammals but other targets, particularly voltage-gated calcium and chloride channels, have been implicated as alternative or secondary sites of action for a subset of pyrethroids. This review summarizes information published during the past decade on the action of pyrethroids on voltage-gated sodium channels as well as on voltage-gated calcium and chloride channels and provides a critical re-evaluation of the role of these three targets in pyrethroid neurotoxicity based on this information.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Allen SL (2010) Regulatory aspects of neurotoxicity assessment. In: Krieger RI (ed) Hayes’ handbook of pesticide toxicology, vol 1, 3rd edn. Elsevier, New York, pp 587–602

    Chapter  Google Scholar 

  • Alves A-M, Symington SB, Lee SH, Clark JM (2010) PKC-dependent phosphorylations modify the action of deltamethrin on rat brain N-type (Cav2.2) voltage-sensitive calcium channel. Pestic Biochem Physiol 97:101–108

    Article  CAS  Google Scholar 

  • Auld VJ, Goldin AL, Krafte DS, Marshall J, Dunn JM, Catterall WA, Lester HA, Davidson N, Dunn RJ (1988) A rat brain Na+ channel α subunit with novel gating properties. Neuron 1:449–461

    Article  PubMed  CAS  Google Scholar 

  • Barnes JM, Verschoyle RD (1974) Toxicity of new pyrethroid insecticide. Nature 248:711

    Article  PubMed  CAS  Google Scholar 

  • Borg JJ, Hancox JC, Spencer CI, Kozlowski RZ (2002) Tefluthrin modulates a novel anionic background conductance (IAB) in guinea-pig ventricular myocytes. Biochem Biophys Res Commun 292:208–215

    Article  PubMed  CAS  Google Scholar 

  • Borg JJ, Hancox JC, Zhang H, Spencer CI, Li H, Kozlowski RZ (2007) Differential pharmacology of the cardiac anionic background current IAB. Eur J Pharmacol 569:163–170

    Article  PubMed  CAS  Google Scholar 

  • Breckenridge CB, Holden L, Sturgess N, Weiner M, Sheets L, Sargent D, Soderlund DM, Choi J-S, Symington S, Clark JM, Burr S, Ray D (2009) Evidence for a separate mechanism of toxicity for the Type I and Type II pyrethroid insecticides. Neurotoxicology 30:S17–S31

    Article  PubMed  CAS  Google Scholar 

  • Brown LD, Narahashi T (1992) Modulation of nerve membrane sodium channel activation by deltamethrin. Brain Res 584:71–76

    Article  PubMed  CAS  Google Scholar 

  • Burr SE, Ray DE (2004) Structure-activity and interaction effects of 14 different pyrethroids on voltage-gated chloride ion channels. Toxicol Sci 77:341–346

    Article  PubMed  CAS  Google Scholar 

  • Cao Z, Shafer TJ, Murray TF (2011) Mechanisms of pyrethroid insecticide-induced stimulation of calcium influx into neocortical neurons. J Pharmacol Exp Ther 336:197–205

    Article  PubMed  CAS  Google Scholar 

  • Catterall WA, Goldin AL, Waxman SG (2005) International Union of Pharmacology. XLVII. Nomenclature and structure-function relationships of voltage-gated sodium channels. Pharmacol Rev 57:397–409

    Article  PubMed  CAS  Google Scholar 

  • Choi J-S, Soderlund DM (2002) Actions of cismethrin, deltamethrin and cyclosporin A on Nav1.8 sodium channels expressed in Xenopus oocytes. Soc Neurosci Abstr 28:743.720

    Google Scholar 

  • Choi J-S, Soderlund DM (2004) Cylcosporin A and deltamethrin block the downregulation of Nav1.8 sodium channels expressed in Xenopus oocytes. Neurosci Lett 367:389–393

    Article  PubMed  CAS  Google Scholar 

  • Choi J-S, Soderlund DM (2006) Structure-activity relationships for the action of 11 pyrethroid insecticides on rat Nav1.8 sodium channels expressed in Xenopus oocytes. Toxicol Appl Pharmacol 211:233–244

    Article  PubMed  CAS  Google Scholar 

  • Culliford SJ, Borg JJ, O’Brien MJ, Kozlowski RZ (2004) Differential effects of pyrethroids on volume-sensitive anion and organic osmolyte pathways. Clin Exp Pharmacol Physiol 31:134–144

    Article  PubMed  CAS  Google Scholar 

  • de Weille JR, Vijverberg HPM, Narahashi T (1988) Interactions of pyrethroids and octylguanidine with sodium channels of squid giant axons. Brain Res 445:1–11

    Article  PubMed  Google Scholar 

  • Dong K (2007) Insect sodium channels and insecticide resistance. Invert Neurosci 7:17–30

    Article  PubMed  CAS  Google Scholar 

  • Du Y, Lee J-E, Nomura Y, Zhang T, Zhorov B, Dong K (2009) Identification of a cluster of residues in transmembrane 6 of domain III of the cockroach sodium channel essential for the action of pyrethroid insecticides. Biochem J 419:377–385

    Article  PubMed  CAS  Google Scholar 

  • Elliott M, Farnham AW, Janes NF, Needham PH, Pulman DA (1974) Synthetic insecticide with a new order of activity. Nature 248:710–711

    Article  PubMed  CAS  Google Scholar 

  • Felts PA, Yokoyama S, Dib-Hajj S, Black JA, Waxman SG (1997) Sodium channel α-subunit mRNAs I, II, III, NaG, Na6 and hNE (PN1): different expression patters in developing rat nervous system. Mol Brain Res 45:71–82

    Article  PubMed  CAS  Google Scholar 

  • Gammon DW, Brown MA, Casida JE (1981) Two classes of pyrethroid action in the cockroach. Pestic Biochem Physiol 15:181–191

    Article  CAS  Google Scholar 

  • Ginsburg KS, Narahashi T (1993) Differential sensitivity of tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels to the insecticide allethrin in rat dorsal root ganglion neurons. Brain Res 627:239–248

    Article  PubMed  CAS  Google Scholar 

  • Goldin AL (2001) Resurgence of sodium channel research. Annu Rev Physiol 63:871–894

    Article  PubMed  CAS  Google Scholar 

  • Goldin AL (2003) Mechanisms of sodium channel inactivation. Curr Opin Neurobiol 13:284–290

    Article  PubMed  CAS  Google Scholar 

  • Hildebrand ME, McRory JE, Snutch TP, Stea A (2004) Mammalian voltage-gated calcium channels are potently blocked by the pyrethroid insecticide allethrin. J Pharmacol Exp Ther 308:805–813

    Article  PubMed  CAS  Google Scholar 

  • Hille B (1977) Local anesthetics: hydrophilic and hydrophobic pathways for the drug-receptor interaction. J Gen Physiol 67:497–515

    Article  Google Scholar 

  • Hu W, Tian C, Yang M, Hou H, Shu Y (2009) Distinct contributions of Nav1.6 and Nav1.2 in action potential initiation and backpropagation. Nat Neurosci 12:996–1002

    Article  PubMed  CAS  Google Scholar 

  • Jentsch TJ, Stein V, Weinreich F, Zdebik AA (2001) Molecular structure and physiological function of chloride channels. Physiol Rev 82:503–568

    Google Scholar 

  • Kadala A, Charreton M, Jakob I, Le Conte Y, Collet C (2011) A use-dependent sodium current modification induced by type I pyrethroid insecticides in honeybee antennal olfactory neurons. Neurotoxicology 32:320–330

    Article  PubMed  CAS  Google Scholar 

  • Lawrence LJ, Casida JE (1982) Pyrethroid toxicology: mouse intracerebral structure-toxicity relationships. Pestic Biochem Physiol 18:9–14

    Article  CAS  Google Scholar 

  • Lee SH, Soderlund DM (2001) The V410 M mutation associated with pyrethroid resistance in Heliothis virescens reduces the pyrethroid sensitivity of house fly sodium channels expressed in Xenopus oocytes. Insect Biochem Mol Biol 31:19–29

    Article  PubMed  CAS  Google Scholar 

  • Li H, Zhang H, Hancox JC, Kozlowski RZ (2007) An outwardly rectifying anionic background current in atrial myocytes from the human heart. Biochem Biophys Res Commun 359:765–770

    Article  PubMed  CAS  Google Scholar 

  • Lipkind GM, Fozzard HA (2000) KcsA crystal structure as framework for a molecular model of the Na+ channel pore. Biochemistry 39:8161–8170

    Article  PubMed  CAS  Google Scholar 

  • Lombet A, Mourre C, Lazdunski M (1988) Interactions of insecticides of the pyrethroid family with specific binding sites on the voltage-dependent sodium channel from mammalian brain. Brain Res 459:44–53

    Article  PubMed  CAS  Google Scholar 

  • Maritzen T, Blanz J, Jentsch T (2006) Physiological functions of the CLC chloride transport proteins. Adv Mol Cell Biol 38:9–57

    Article  Google Scholar 

  • Meacham CA, Brodfuehrer PD, Watkins JA, Shafer TJ (2008) Developmentally-regulated sodium channel subunits are differentially sensitive to α-cyano containing pyrethroids. Toxicol Appl Pharmacol 231:273–281

    Google Scholar 

  • Meadows LS, Isom LL (2005) Sodium channels as macromolecular complexes: implications for inherited arrhythmia syndromes. Cardiovasc Res 67:448–458

    Article  PubMed  CAS  Google Scholar 

  • Naeher LP, Tulve NS, Egeghy PP, Barr DB, Adetona O, Fortmann RC, Needham LL, Bozeman E, Hilliard A, Sheldon LS (2010) Organophosphorus and pyrethroid insecticide urinary metabolite concentrations in young children living in a southeastern United States city. Sci Total Environ 408:1145–1153

    Article  PubMed  CAS  Google Scholar 

  • O’Reilly AO, Khambay BPS, Williamson MS, Field LM, Wallace BA, Davies TGE (2006) Modelling insecticide binding sites at the voltage-gated sodium channel. Biochem J 396:255–263

    Article  PubMed  Google Scholar 

  • Ostrea EM Jr, Bielawski DM, Poecion NC Jr, Corrion M, Villaneuva-Uy E, Bernardo RC, Jin Y, Janisse JL, Ager JW (2009) Combined analysis of prenatal (maternal hair and blood) and neonatal (infant hair, cord blood and meconium) matrices to detect fetal exposure of environmental pesticides. Environ Res 109:116–122

    Article  PubMed  CAS  Google Scholar 

  • Pickett JA (2004) New opportunities in neuroscience, but a great danger that some may be lost. In: Beadle DJ, Mellor IR, Usherwood PNR (eds) Neurotox ‘03: neurotoxicological targets from functional genomics and proteomics. Society of Chemical Industry, London, pp 1–10

    Google Scholar 

  • Power LE, Sudakin DL (2007) Pyrethrin and pyrethroid exposures in the United States: a longitudinal analysis of incidents reported to poison centers. J Med Toxicol 3:94–99

    Article  PubMed  Google Scholar 

  • Ranson H, N’Guessan R, Lines J, Moiroux N, Nkuni Z, Corbel V (2011) Pyrethroid resistance in African anopheles mosquitoes: what are the implications for malaria control? Trends Parasitol 27:91–98

    Article  PubMed  CAS  Google Scholar 

  • Rush AM, Cummins TR, Waxman SG (2007) Multiple sodium channels and their role in electrogenesis within dorsal root ganglion neurons. J Physiol 579:1–14

    Article  PubMed  CAS  Google Scholar 

  • Salgado VL, Narahashi T (1993) Immobilization of sodium channel gating charge in crayfish giant axons by the insecticide fenvalerate. Mol Pharmacol 43:626–634

    PubMed  CAS  Google Scholar 

  • Sardini A (2006) Cell volume homeostasis: the role of volume-sensitive chloride channels. Adv Mol Cell Biol 38:199–214

    Article  Google Scholar 

  • Shafer TJ, Meyer DA (2004) Effects of pyrethroids on voltage-sensitive calcium channels: a critical evaluation of strengths, weaknesses, data needs, and relationship to assessment of cumulative neurotoxicity. Toxicol Appl Pharmacol 196:303–318

    Article  PubMed  CAS  Google Scholar 

  • Shafer TJ, Meyer DA, Crofton KM (2005) Developmental neurotoxicity of pyrethroid insecticides: critical review and future research needs. Environ Health Perspect 113:123–136

    Article  PubMed  CAS  Google Scholar 

  • Shah BS, Stevens EB, Pinnock RD, Dixon AK, Lee K (2001) Developmental expression of the novel voltage-gated sodium channel auxiliary subunit β3, in rat CNS. J Physiol 534:763–776

    Article  PubMed  CAS  Google Scholar 

  • Shrivastava IH, Durell SR, Guy HR (2004) A model of voltage gating developed using the KvAP channel crystal structure. Biophys J 87:2255–2270

    Article  PubMed  CAS  Google Scholar 

  • Smith TJ, Soderlund DM (1998) Action of the pyrethroid insecticide cypermethrin on rat brain IIa sodium channels expressed in Xenopus oocytes. NeuroToxicology 19:823–832

    PubMed  CAS  Google Scholar 

  • Smith TJ, Soderlund DM (2001) Potent actions of the pyrethroid insecticides cismethrin and cypermethrin on rat tetrodotoxin-resistant peripheral nerve (SNS/PN3) sodium channels expressed in Xenopus oocytes. Pestic Biochem Physiol 70:52–61

    Article  CAS  Google Scholar 

  • Smith TJ, Lee SH, Ingles PJ, Knipple DC, Soderlund DM (1997) The L1014F point mutation in the house fly Vssc1 sodium channel confers knockdown resistance to pyrethroids. Insect Biochem Mol Biol 27:807–812

    Article  PubMed  CAS  Google Scholar 

  • Smith TJ, Ingles PJ, Soderlund DM (1998) Actions of the pyrethroid insecticides cismethrin and cypermethrin on house fly Vssc1 sodium channels expressed in Xenopus oocytes. Arch Insect Biochem Physiol 38:126–136

    Article  PubMed  CAS  Google Scholar 

  • Soderlund DM (2005) Sodium channels. In: Gilbert L, Iatrou K, Gill S (eds) Comprehensive molecular insect science, vol 5. Elsevier, New York, pp 1–24

    Chapter  Google Scholar 

  • Soderlund DM (2008) Pyrethroids, knockdown resistance and sodium channels. Pest Manag Sci 64:610–616

    Article  PubMed  CAS  Google Scholar 

  • Soderlund DM (2010a) State-dependent modification of voltage-gated sodium channels by pyrethroids. Pestic Biochem Physiol 97:78–86

    Article  PubMed  CAS  Google Scholar 

  • Soderlund DM (2010b) Toxicology and mode of action of pyrethroid insecticides. In: Krieger RI (ed) Hayes’ handbook of pesticide toxicology, vol 2, 3rd edn. Elsevier, New York, pp 1665–1686

    Chapter  Google Scholar 

  • Soderlund DM, Lee SH (2001) Point mutations in homology domain II modify the sensitivity of rat Nav1.8 sodium channels to the pyrethroid cismethrin. Neurotoxicology 22:755–765

    Article  CAS  Google Scholar 

  • Soderlund DM, Clark JM, Sheets LP, Mullin LS, Piccirillo VJ, Sargent D, Stevens JT, Weiner ML (2002) Mechanisms of pyrethroid toxicity: implications for cumulative risk assessment. Toxicology 171:3–59

    Article  PubMed  CAS  Google Scholar 

  • Song J-H, Nagata K, Tatebayashi H, Narahashi T (1996) Interactions of tetramethrin, fenvalerate and DDT at the sodium channel in rat dorsal root ganglion neurons. Brain Res 708:29–37

    Article  PubMed  CAS  Google Scholar 

  • Spencer CI, Sham JSK (2005) Mechanisms underlying the effects of the pyrethroid tefluthrin on action potential durations in isolated rat ventricular myocytes. J Pharmacol Exp Ther 315:16–23

    Article  PubMed  CAS  Google Scholar 

  • Spencer CI, Yuill KH, Borg JJ, Hancox JC, Kozlowski RZ (2001) Action of pyrethroid insecticides on sodium currents, action potentials, and contractile rhythm in isolated mammalian ventricular myocytes and perfused hearts. J Pharmacol Exp Ther 298:1067–1082

    PubMed  CAS  Google Scholar 

  • Symington SB, Clark JM (2005) Action of deltamethrin on N-type (Cav2.2) voltage-sensitive calcium channels in rat brain. Pestic Biochem Physiol 82:1–15

    Article  CAS  Google Scholar 

  • Symington SB, Frisbie RK, Kim H-J, Clark JM (2007a) Mutation of threonine-422 to glutamic acid mmics the phosphorylation state and alters the action of deltamethrin on Cav2.2. Pestic Biochem Physiol 88:312–320

    Article  CAS  Google Scholar 

  • Symington SB, Frisbie RK, Lu KD, Clark JM (2007b) Action of cismethrin and deltamethrin on functional attributes of isolated presynaptic nerve terminals from rat brain. Pestic Biochem Physiol 87:172–181

    Article  CAS  Google Scholar 

  • Symington SB, Frisbie RK, Clark JM (2008) Characterization of 11 commercial pyrethroids on the functional attributes of rat brain synaptosomes. Pestic Biochem Physiol 92:61–69

    Article  CAS  Google Scholar 

  • Symington SB, Hodgdon HE, Frisbie RK, Clark JM (2011) Binary mixtures of pyrethroids produce differential effects on Ca2+ influx and glutamate release at isolated presynaptic nerve terminals from rat brain. Pestic Biochem Physiol 99:131–139

    Article  CAS  Google Scholar 

  • Tabarean IV, Narahashi T (1998) Potent modulation of tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels by the Type II pyrethroid deltamethrin. J Pharmacol Exp Ther 284:958–965

    PubMed  CAS  Google Scholar 

  • Tabarean IV, Narahashi T (2001) Kinetics of modulation of tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels by tetramethrin and deltamethrin. J Pharmacol Exp Ther 299:988–997

    PubMed  CAS  Google Scholar 

  • Tan J, Soderlund DM (2009) Human and rat Nav1.3 voltage-gated sodium channels differ in inactivation properties and sensitivity to the pyrethroid insecticide tefluthrin. Neurotoxicology 30:81–89

    Article  PubMed  CAS  Google Scholar 

  • Tan J, Soderlund DM (2010) Divergent actions of the pyrethroid insecticides S-bioallethrin, tefluthrin, and deltamethrin on rat Nav1.6 sodium channels. Toxicol Appl Pharmacol 247:229–237

    Article  PubMed  CAS  Google Scholar 

  • Tan J, Soderlund DM (2011) Action of tefluthrin on rat Nav1.7 voltage-gated sodium channels expressed in Xenopus oocytes. Pestic Biochem Physiol. doi:10.1016/j.pestbp.2011.06.001

  • Tan J, Liu Z, Wang R, Huang ZY, Chen AC, Gurevitz M, Dong K (2005) Identification of amino acid residues in the insect sodium channel critical for pyrethroid binding. Mol Pharmacol 67:513–522

    Article  PubMed  CAS  Google Scholar 

  • Tan J, Choi J-S, Soderlund DM (2008) Action of pyrethroid insecticides on rat Nav1.6 sodium channels expressed in Xenopus oocytes. Toxicol 97: Abstract 2274

  • Tatebayashi H, Narahashi T (1994) Differential mechanism of action of the pyrethroid tetramethrin on tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels. J Pharmacol Exp Ther 270:595–603

    PubMed  CAS  Google Scholar 

  • Thimmapaya R, Neelands T, Niforatos W, Davis-Taber RA, Choi W, Putman CB, Kroeger PE, Packer J, Gopalakrishnan M, Faltynek CR, Surowy CS, Scott VE (2005) Distribution and functional characterization of human Nav1.3 splice variants. Eur J Neurosci 22:1–9

    Article  PubMed  CAS  Google Scholar 

  • Trainer VL, McPhee JC, Boutelet-Bochan H, Baker C, Scheuer T, Babin D, Demoute J-P, Guedin D, Catterall WA (1997) High affinity binding of pyrethroids to the α subunit of brain sodium channels. Mol Pharmacol 51:651–657

    PubMed  CAS  Google Scholar 

  • Ulbricht W (2005) Sodium channel inactivation: molecular determinants and modulation. Physiol Rev 85:1271–1301

    Article  PubMed  CAS  Google Scholar 

  • Usherwood PNR, Davies TGE, Mellor IR, O’Reilly AO, Peng F, Vais H, Khambay BPS, Field LM, Williamson MS (2007) Mutations in DIIS5 and the DIIS4–5 linker of Drosophila melanogaster sodium channel define binding domains for pyrethroids and DDT. FEBS Lett 581:5485–5492

    Article  PubMed  CAS  Google Scholar 

  • Vais H, Atkinson S, Eldursi N, Devonshire AL, Williamson MS, Usherwood PNR (2000a) A single amino acid change makes a rat neuronal sodium channel highly sensitive to pyrethroid insecticides. FEBS Lett 470:135–138

    Article  PubMed  CAS  Google Scholar 

  • Vais H, Williamson MS, Goodson SJ, Devonshire AL, Warmke JW, Usherwood PNR, Cohen CJ (2000b) Activation of Drosophila sodium channels promotes modification by deltamethrin: reductions in affinity caused by knock-down resistance mutations. J Gen Physiol 115:305–318

    Article  PubMed  CAS  Google Scholar 

  • Vais H, Williamson MS, Devonshire AL, Usherwood PNR (2001) The molecular interactions of pyrethroid insecticides with insect and mammalian sodium channels. Pest Manag Sci 57:877–888

    Article  PubMed  CAS  Google Scholar 

  • Vais H, Atkinson S, Pluteanu F, Goodson SJ, Devonshire AL, Williamson MS, Usherwood PNR (2003) Mutations of the para sodium channel of Drosophila melanogaster identify putative binding sites for pyrethroids. Mol Pharmacol 64:914–922

    Article  PubMed  CAS  Google Scholar 

  • Verschoyle RD, Aldridge WN (1980) Structure-activity relationships of some pyrethroids in rats. Arch Toxicol 45:325–329

    Article  PubMed  CAS  Google Scholar 

  • Verschoyle RD, Barnes JM (1972) Toxicity of natural and synthetic pyrethrins to rats. Pestic Biochem Physiol 2:308–311

    Article  CAS  Google Scholar 

  • Wang S-Y, Barile M, Wang GK (2001) A phenylalanine residue at segment D3–S6 in Nav1.4 voltage-gated Na + channels is critical for pyrethroid action. Mol Pharmacol 60:620–628

    PubMed  CAS  Google Scholar 

  • Wang S-Y, Mitchell J, Moczydlowski E, Wang GK (2004) Block of inactivation-deficient Na + channels bo local anesthetics in stably transfected mammalian cells: evidence for drug binding along the activation pathway. J Gen Physiol 124:691–701

    Article  PubMed  CAS  Google Scholar 

  • Weiner ML, Nemec M, Sheets L, Sargent D, Breckenridge C (2009) Comparative functional observational battery of twelve commercial pyrethroid insecticides in male rats following acute oral exposure. Neurotoxicology 30:S1–S16

    Article  PubMed  CAS  Google Scholar 

  • Whitaker WRJ, Clare JJ, Powell AJ, Chen YH, Faull RLM, Emson PC (2000) Distribution of voltage-gated sodium channel α-subunit and β-subunit mRNAs in human hippocampal formation, cortex, and cerebellum. J Comp Neurol 422:123–139

    Article  PubMed  CAS  Google Scholar 

  • Whitaker WRJ, Faull RLM, Waldvogel HJ, Plumpton CJ, Emson PC, Clare JJ (2001) Comparative distribution of voltage-gated sodium channel proteins in human brain. Mol Brain Res 88:37–53

    Article  PubMed  CAS  Google Scholar 

  • Wu S-N, Wu Y-H, Chen B-S, Liu Y-C (2009) Underlying mechanism of action of tefluthrin, a pyrethroid insecticide, on voltage-gated ion currents and on action currents in pituitary tumor (GH3) cells and GnRH-secreting (GT1–7) neurons. Toxicology 2009:70–77

    Article  Google Scholar 

  • Zhao Y, Yarov-Yarovoy V, Scheuer T, Catterall WA (2004) A gating hinge in Na+ channels: a molecular switch for electrical signaling. Neuron 41:859–865

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

Research that was conducted in the author’s laboratory and the preparation of this review were supported by grants from National Institute of Environmental Health Sciences, National Institutes of Health (R01-ES08962 and R01-ES013686) and the Pyrethroid Working Group, a consortium of firms (Bayer CropScience, DuPont Crop Protection, FMC Corporation, Syngenta Crop Protection Inc., and Valent Corporation) that market pyrethroid-based insecticide products in the United States. The contents of this paper are solely the responsibility of the author and do not necessarily represent the official views of any of the sponsors.

Author information

Authors and Affiliations

  1. Department of Entomology, New York State Agricultural Experiment Station, Cornell University, Geneva, NY, 14456, USA

    David M. Soderlund

Authors
  1. David M. Soderlund
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to David M. Soderlund.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Soderlund, D.M. Molecular mechanisms of pyrethroid insecticide neurotoxicity: recent advances. Arch Toxicol 86, 165–181 (2012). https://doi.org/10.1007/s00204-011-0726-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00204-011-0726-x

Keywords

Search

Navigation