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Ion channels: molecular targets of neuroactive insecticides

Abstract

Many of the insecticides in current use act on molecular targets in the insect nervous system. Recently, our understanding of these targets has improved as a result of the complete sequencing of an insect genome, i.e., Drosophila melanogaster. Here we examine the recent work, drawing on genetics, genomics and physiology, which has provided evidence that specific receptors and ion channels are targeted by distinct chemical classes of insect control agents. The examples discussed include, sodium channels (pyrethroids, p,p′-dichlorodiphenyl-trichloroethane (DDT), dihydropyrazoles and oxadiazines); nicotinic acetylcholine receptors (cartap, spinosad, imidacloprid and related nitromethylenes/nitroguanidines); γ-aminobutyric acid (GABA) receptors (cyclodienes, γ-BHC and fipronil) and L-glutamate receptors (avermectins). Finally, we have examined the molecular basis of resistance to these molecules, which in some cases involves mutations in the molecular target, and we also consider the future impact of molecular genetic technologies in our understanding of the actions of neuroactive insecticides.

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References

  • Adams MD, Celniker SE, Holt RA, Evans CA, Gocayne JD, Amanatides PG, Scherer et al (2000) The genome sequence of Drosophila melanogaster. Science 287:2185–2195

    Article  PubMed  Google Scholar 

  • Adelsberger H, Lepier A, Dudel J (2000) Activation of rat recombinant α1β2γ2S GABA A receptor by the insecticide ivermectin. Eur J Pharmacol 394:163–170

    Article  Google Scholar 

  • Anstead JA, Williamson MS, Denholm I (2005) Evidence for multiple origins of identical insecticide resistance mutations in the aphid Myzus persicae. Insect Biochem Mol Biol 35:249–256

    Article  Google Scholar 

  • Bettini S, D’Ajello V, Maroli M (1973) Cartap activity on the cockroach nervous system and neuromuscular transmission. Pestic Biochem Physiol 3:100–205

    Article  Google Scholar 

  • Bloomquist JR (1996) Ion channels as targets for insecticides. Ann Rev Entomol 1:163–190

    Article  Google Scholar 

  • Bowery NG, Collins JF, Hill RG (1976) Bicyclic phosphorus esters that are potent convulsants and GABA antagonists. Nature 261:601–603

    Article  Google Scholar 

  • Breer H, Sattelle DB (1987) Molecular properties and functions of insect acetylcholine receptors. J Insect Physiol 33:771–790

    Article  Google Scholar 

  • Bret BL, Larson LL, Schoonover JR, Sparks TC, Thompson GD (1997) Biological properties of spinosad. Down Earth 52:6–13

    Google Scholar 

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

    Article  Google Scholar 

  • Buckingham SD, Matsuda K, Hosie AM, Baylis HA, Squire MD, Lansdell SJ, Millar NS, Sattelle DB (1996) Wild-type and insecticide-resistant homo-oligomeric GABA receptors of Drosophila melanogaster stably expressed in a drosophila cell line. Neuropharmacol 35:1393–1401

    Article  Google Scholar 

  • Buckingham SD, Lapied B, Le Corronc H, Grolleau F, Sattelle DB (1997) Imidacloprid actions on insect neuronal acetylcholine receptors. J Exp Biol 200:2685–2692

    PubMed  Google Scholar 

  • Castillo M, Mulet J, Gutiérrez LM, Ortiz JA, Castelan F, Gerber S, Sala S et al (2005) Dual role of the RIC-3 protein in trafficking of serotonin and nicotinic acetylcholine receptors. J Biol Chem 280:27062–27068

    Article  Google Scholar 

  • Catterall WA (2000) From ionic currents to molecular mechanisms: the structure and function of voltage-gated sodium channels. Neuron 26:13–25

    Article  Google Scholar 

  • Catterall WA, Goldin AL, Waxman SG (2003) International Union of Pharmacology XXXIX. Compendium of voltage-gated ion channels: sodium channels. Pharmacol Rev 55:575–578

    Article  Google Scholar 

  • Cestèle S, Catterall WA (2000) Molecular mechanisms of neurotoxin action on voltage-gated sodium channels. Biochimie 82:883–892

    Article  Google Scholar 

  • Cleland TA (1996) Inhibitory glutamate receptor channels. Mol Neurobiol 13:97–136

    PubMed  Google Scholar 

  • Colliot F, Kukorowski KA, Robert DA (1992) Fipronil: a new soil and foliar broad spectrum insecticide. In: Proceedings of the Brighton crop protection conferences-pests and diseases, pp 29–34

  • Courjaret R, Lapied B (2001) Complex intracellular messenger pathways regulate one type of neuronal α-bungarotoxin-resistant nicotinic acetylcholine receptors expressed in insect neurosecretory cells (Dorsal Unpaired Median neurons). Mol Pharmacol 60:80–91

    PubMed  Google Scholar 

  • Cully DF, Wilkinson H, Vassilatis DK, Etter A, Arena JP (1996a) Molecular biology and electrophysiology of glutamate-gated chloride channels of invertebrates. Parasitol 113:S191–S200

    Google Scholar 

  • Cully DF, Paress PS, Liu KK, Schaeffer JM, Arena JP (1996b) Identification of a Drosophila melanogaster glutamate-gated chloride channel sensitive to the antiparasitic agent avermectin. J Biol Chem 271:20187–20191

    Article  Google Scholar 

  • Deecher DC, Soderlund DM (1991) RH 3421, an insecticidal dihydropyrazole, inhibits sodium channel-dependant sodium uptake in mouse brain preparations. Pest Biochem Physiol 39:130–137

    Article  Google Scholar 

  • Déglise P, Grünewald B, Gauthier M (2002) The insecticide imidacloprid is a partial agonist of the nicotinic receptor of honeybee Kenyon cells. Neurosci Lett 321:13–16

    Article  PubMed  Google Scholar 

  • Dent JA, Smith MN, Vassilatis DK, Avery L (2000) The genetics of ivermectin resistance in Caenorhabditis elegans. Proc Natl Acad Sci USA 97:2674–2679

    Article  Google Scholar 

  • Duce IR, Scott RH (1985) Actions of dihydroavermectin B1a on insect muscle. Br J Pharmacol 85:395–401

    PubMed  Google Scholar 

  • ffrench-Constant RH, Mortlock DP, Schaffer CD, MacIntyre RJ, Roush RT (1991) Molecular cloning and transformation of cyclodiene resistance in Drosophila: an invertebrate γ-aminobutyric acid subtype A receptor locus. Proc Natl Acad Sci USA 88:7209–7213

    PubMed  Google Scholar 

  • ffrench-Constant RH, Rocheleau TA, Steichen JC, Chalmers AE (1993) A point mutation in Drosophila GABA receptor confers insecticide resistance. Nature 363:449–451

    Article  Google Scholar 

  • Gardner MJ, Hall N, Fung E, White O, Bessiman M, Hyman RW, Carlton J et al (2002) Genome sequence of the human malaria parasite Plasmodium falciparum. Nature 419:498–511

    Article  Google Scholar 

  • Gisselmann G, Plonka J, Pusch H, Hatt H (2004) Drosophila melanogaster GRD and LCCH3 subunits form heteromultimeric GABA-gated cation channels. Br J Pharmacol 142:409–413

    Article  Google Scholar 

  • Grauso M, Reenan RA, Culetto E, Sattelle DB (2002) Novel putative nicotinic acetylcholine receptor subunit genes, Dα5, Dα6 and Dα7, in Drosophila melanogaster identify a new and highly conserved target of ADAR-mediated A to I pre-mRNA editing. Genetics 160:1519–1533

    PubMed  Google Scholar 

  • Grolleau F, Sattelle DB (2000) Single channel analysis of the blocking actions of BIDN and Fipronil on a Drosophila melanogaster GABA receptor (RDL) stably expressed in a Drosophila cell line. Br J Pharmacol 30:1833–1842

    Article  Google Scholar 

  • Gundelfinger E (1992) How complex is the nicotinic receptor system of insects? Trends Neurosci 15:206–211

    Article  Google Scholar 

  • Gundelfinger ED, Schulz R (2000) Insect nicotinic acetylcholine receptors: genes, structure, physiological and pharmacological properties. In: Clementi F, Fornasari D, Gotti C (eds) Neuronal nicotinic receptors. Handbook of experimental pharmacology, vol 144. Springer, Berlin Heidelberg New York, pp 497–521

  • Halevi S, McKay J, Palfreyman M, Yassin L, Eshel M, Jorgensen E, Treinin M (2002) The C. elegans ric-3 gene is required for maturation of nicotinic acetylcholine receptors. EMBO J 21:1012–1020

    Article  Google Scholar 

  • Hanrahan CJ, Palladino MJ, Bonneau LJ, Reenan RA (1999) RNA editing of a Drosophila sodium channel gene. Ann N Y Acad Sci 868:51–56

    PubMed  Google Scholar 

  • Harder HH, Riley SL, McCann SF, Irving SN (1996) DPX-MP062: a novel broad-spectrum, environmentally soft, insect control compound. In: Brighton crop protection conference—pest and diseases, pp 449–454

  • Hitmi A, Coudret A, Barthomeuf C (2000) The production of pyrethrins by plant cells and tissue cultures of Chrysanthemum cinerariaefolium and Tagetes species. Crit Rev Biochem Mol Biol 35:317–337

    Article  Google Scholar 

  • Holt R, Subramanian GM, Halpern A, Sutton GG, Charlab, Nusskern DR, Wincker P et al (2002) The genome sequence of the malaria mosquito Anopheles gambiae. Science 298:129–149

    Google Scholar 

  • Hoopengardner B, Bhalla T, Staker C, Reenan R (2003) Nervous system targets of RNA editing identified by comparative genomics. Science 301:832–836

    Google Scholar 

  • Horoszok L, Raymond V, Sattelle DB, Wostenholme A (2001) GLC-3: a novel Fipronil and BIDN-sensitive, but picrotoxinin-insensitive, L-glutamate-gated chloride channel subunit from Caenorhabditis elegans. Br J Pharmacol 132:1247–1254

    Article  PubMed  Google Scholar 

  • Hosie AM, Aronstein K, Sattelle DB, ffrench-Constant RH (1997) Molecular biology of insect neuronal GABA receptors. TINS 20:578–583

    PubMed  Google Scholar 

  • Hosie AM, Buckingham SD, Presnail JK, Sattelle DB (2001) Alternative splicing of a Drosophila GABA receptor subunit gene identifies determinants of agonist potency. Neuroscience 102:709–714

    Article  Google Scholar 

  • Ikeda T, Zhao X, Nagata K, Kono Y, Shono T, Yeh JZ, Narahashi T (2001) Fipronil modulation of γ-aminobutric acidA receptors in rat dorsal root ganglion neurons. J Pharmacol Exp Ther 296:914–921

    PubMed  Google Scholar 

  • Jones AK, Sattelle DB (2004) Functional genomics of the nicotinic acetylcholine receptor gene family of the nematode, Caenorhabditis elegans. Bioessays 26:39–49

    Article  Google Scholar 

  • Jones AK, Grauso M, Sattelle DB (2005) The nicotinic acetylcholine receptor gene family of the malaria mosquito, Anopheles gambiae. Genomics 85:176–187

    Article  Google Scholar 

  • Kane NS, Hirschberg B, Qion S, Hunt D, Thomas B, Brochu R, Ludmerer SW, Zheng Y, Smith M, Arena JP, Cohen CJ, Schmatz D, Warmke J, Cully DF (2000) Drug resistant Drosophila indicate glutamate-gated chloride channels are targets for the antiparasitics nodulisporic acid and ivermectin. Proc Natl Acad Sci USA 97:13949–13954

    Article  Google Scholar 

  • Karlin A (2002) Emerging structure of the nicotinic acetylcholine receptors. Nature Rev Neuroscience 3:102–114

    Google Scholar 

  • Knipple DC, Doyle KE, Marsella-Merrick PA, Soderlund DM (1994) Tight genetic linkage between the kdr insecticide resistance trait and a voltage-sensitive sodium channel gene in the house fly. Proc Natl Acad Sci USA 91:2483–2487

    PubMed  Google Scholar 

  • Kobayashi T, Nishimura K, Fujita T (1989) Effects of the α-cyano group in the benzyl alcohol moiety on insecticidal and neurophysiological activities of pyrethroid esters. Pestic Biochem Physiol 35:231–243

    Article  Google Scholar 

  • Korenaga S, Ito Y, Ozoe Y, Eto M (1977) The effects of bicyclic phosphate esters on the invertebrate and vertebrate neuro-muscular junctions. Comp Biochem Physiol C 57:95–100

    Article  Google Scholar 

  • Krause RM, Buisson B, Bertrand S, Corringer PJ, Galzi JL, Changeux JP, Bertrand D (1998) Ivermectin: a positive allosteric effector of the alpha 7 neuronal nicotinic acetylcholine receptor. Mol Pharmacol 53:283–294

    PubMed  Google Scholar 

  • Lansdell SJ, Millar NS (2000) Cloning and heterologous expression of Dalpha4, a Drosophila neuronal nicotinic acetylcholine receptor subunit: identification of an alternative exon influencing the efficiency of subunit assembly. Neuropharmacology 39:2604–2614

    Article  Google Scholar 

  • Lapied B, Grolleau F, Sattelle DB (2001) Indoxacarb, an oxadiazine insecticide blocks insect neuronal sodium channels. Br J Pharmacol 132:587–595

    Article  Google Scholar 

  • Laufer J, Roche M, Pelhate M, Elliot M, Janes NF, Sattelle DB (1984) Pyrethroid insecticides: actions of deltamethrin and related compounds on insect axonal sodium channels. J Insect Physiol 30:341–349

    Article  Google Scholar 

  • Laufer J, Pelhate M, Sattelle DB (1985) Actions of pyrethroid insecticides on insect axonal sodium channels. Pest Sci 16:651–661

    Google Scholar 

  • Lee SH, Smith TJ, Knipple DC, Soderlund DM (1999) Mutations in the house fly Vssc1 sodium channel gene associated super-kdr resistance abolish the pyrethroid sensitivity of Vssc1/tipE sodium channels expressed in Xenopus oocytes. Insect Biochem Mol Biol 29:185–94

    Article  Google Scholar 

  • Lee SH, Smith TJ, Ingles PJ, Soderlund DM (2000) Cloning and functional characterization of a putative sodium channel auxiliary subunit gene from the house fly (Musca domestica). Insect Biochem Mol Biol 30:479–487

    Article  Google Scholar 

  • Lindstrom J (2000) The structure of neuronal nicotinic receptors. In: Clementi F, Fornasari D, Gotti C (eds) Neuronal nicotinic receptors. Handbook of experimental pharmacology, vol 144. Springer, Berlin Heidelberg New York, pp 101–162

  • Littleton JT, Ganetzky B (2000) Ion channels and synaptic organisation: analysis of the Drosophila genome. Neuron 26:35–43

    Article  Google Scholar 

  • Liu Z, Tan J, Valles SM, Dong K (2002) Synergistic interaction between two cockroach sodium channel mutation and a tobacco budworm sodium channel mutation in reducing channel sensitivity to a pyrethroid insecicide. Insect Biochem Mol Biol 32:397–404

    Article  Google Scholar 

  • Liu Z, Williamson MS, Lansdell SJ, Denholm I, Han Z, Millar NS (2005) A nicotinic acetylcholine receptor mutation conferring target-site resistance to imidacloprid in Nilaparvata lugens (brown planthopper). Proc Natl Acad Sci USA 102:8420–8425

    Article  Google Scholar 

  • Ludmerer SW, Warren VA, Williams BS, Zheng Y, Hunt DC, Ayer MB, Wallace MA, Chaudhary AG, Egan MA., Meinke PT, Dean DC, Garcia ML, Cully DF, Smith McH M (2002) Ivermectin and nodulisporic acid receptors in Drosophila melanogaster contain both γ-aminobutyric acid-gated Rdl and glutamate-gated GluClα chloride channel subunits. Biochemistry 41:6548–6560

    Article  PubMed  Google Scholar 

  • Lum L, Yao S, Mozer B, Rovescalli A, Von Kessler D, Nirenberg M, Beachey PA (2003) Identification of hedgehog pathway signalling components by RNAi in Drosophila cultured cells. Science 299:2039–2045

    Google Scholar 

  • Martin RL, Pittendrigh B, Liu J, Reenan R, ffrench-Constant R, Hanck DA (2000) Point mutations in domain III of a Drosophila neuronal Na channel confer resistance to allethrin. Insect Biochem Mol Biol 30:1051–1059

    Article  Google Scholar 

  • Massoulié L, Pezzementi L, Bon S, Krejci E, Vallette FM (1993) Molecular and cellular biology of cholinesterases. Prog Neurobiol 41:31–91

    Article  Google Scholar 

  • Matsuda K, Buckingham SD, Kleier D, Rauh JJ, Grauso M, Sattelle DB (2001) Neonicotinoids: insecticides acting on insect nicotinic acetylcholine receptors. TIPS 22:573–580

    PubMed  Google Scholar 

  • Matsumura F, Ghiasuddin SM (1983) Evidence for similarities between cyclodiene type insecticides and picrotoxinin in their action mechanisms. J Environ Sci Health B 18:1–14

    PubMed  Google Scholar 

  • Miyazaki N, Ohyama K, Dunlap DY, Matsumara F (1996) Cloning and sequencing of the para-type sodium channel gene from susceptible and kdr resistant German cockroaches (Blattela germanica) and the house fly (Musca domestica). Mol Gen Genet 252:61–68

    Article  Google Scholar 

  • Mongan NP, Jones AK, Smith GR, Sansom MSP, Sattelle DB (2002) Novel α7-like nicotinic acetylcholine receptor a subunits in the nematode Caenorhabditis elegans. Prot Sci 11:1162–1171

    Article  Google Scholar 

  • Morgan K, Stevens EB, Shah B, Cox PJ, Dixon AK, Lee K, Pinnock RD et al (2000) β3: an additional auxiliary subunit of the voltage-sensitive sodium channel that modulates channel gating with distinct kinetics. Proc Natl Acad Sci USA 97:2308–2313

    Article  Google Scholar 

  • Nagata K, Iwanaga Y, Shono T, Narahashi T (1997) Modulation of the neuronal nicotinic acetylcholine receptor channel by imidacloprid and cartap. Pest Biochem Physiol 59:119–128

    Article  Google Scholar 

  • Narahashi T (1992) Nerve membrane Na+ channels as targets of insecticides. Trends Pharmacol Sci 13:236–241

    Article  Google Scholar 

  • Narahashi T (1996) Neuronal ion channels as the targets of insecticides. Pharmacol Toxicol 79:1–14

    PubMed  Google Scholar 

  • Narahashi T (2000) Neuroreceptors and ion channels as the basis for drug action: past present and future. J Pharm Exp Ther 294:1–26

    Google Scholar 

  • Ozoe Y, Mochida K, Eto M (1982) Binding of toxic bicyclic phosphates to rat brain synaptic membrane fractions. Agric Biol Chem 46:2521–2526

    Google Scholar 

  • Park Y, Taylor MF, Feyereisen R (1997) A valine 421 to methionine mutation in IS6 of the hscp voltage-gated sodium channel associated with pyrethroid resistance in Heliothis virescens F. Biochem Biophys Res Commun 239(3):688–691

    Article  Google Scholar 

  • Pittendrigh B, Reenan R, ffrench-Constant RH, Ganetzky B (1997) Point mutations in the Drosophila sodium channel gene para associated with resistance to DDT and pyrethroid insecticides. Mol Gen Genet 256:602–610

    Article  Google Scholar 

  • Ratra GS, Casida JE (2001) GABA receptor subunit composition relative to insecticide potency and selectivity. Toxicol Lett 122:215–222

    Article  Google Scholar 

  • Rauh JJ, Lummis SCR, Sattelle DB (1990) Pharmacological and biochemical properties of insect GABA receptors. Trends Pharmacol Sci 11:325–329

    Article  PubMed  Google Scholar 

  • Raymond-Delpech V, Ihara M, Coddou C, Matsuda K, Sattelle DB (2003) Actions of nereistoxin on recombinant neuronal nicotinic acetylcholine receptors expressed in Xenopus laevis oocytes. Invert Neurosci 5:29–35

    Article  Google Scholar 

  • Raymond-Delpech V, Towers PR, Sattelle DB (2004) Gene silencing of selective calcium signalling molecules in a Drosophila cell line using RNA interference. Cell Calcium 35:131–139

    Article  Google Scholar 

  • Raymond V, Sattelle DB (2002) Novel animal-health drug targets from ligand-gated chloride channels. Nature Drug Discover 1:427–436

    Article  Google Scholar 

  • Rohrer SP, Birzin ET, Costa SD, Arena JP, Hayes EC, Schaeffer JM (1995) Identification of neuron-specific ivermectin binding sites in Drosophila melanogaster and Schistocerca americana. Insect Biochem Mol Biol 25:11–17

    Article  Google Scholar 

  • Sakai M, Sato Y (1971) Metabolic conversion of the nereistoxin-related compounds into nereistoxin as a factor of their insecticidal action. In: Abstracts in 2nd International Congress Pest Chemistry, Tel Aviv

  • Salgado VL (1992) Slow voltage-dependant block of sodium channels in crayfish nerve by dihydropyrazole insecticides. Mol Pharmacol 41:120–126

    PubMed  Google Scholar 

  • Salgado VL (1998) Studies on the mode of action of spinosad: insect symptoms and physiological correlates. Pestic Biochem Physiol 60:91–102

    Article  Google Scholar 

  • Salgado VL, Saar R (2004) Desensitizing and non-desensitizing subtypes of α-bungarotoxin-sensitive nicotinic acetylcholine receptors in cockroach neurons. J Insect Physiol 50:867–879

    Article  Google Scholar 

  • Salgado VL, Sheets JJ, Watson GB, Schmidt AL (1998) Studies on the mode of action of spinosad: the internal effective concentrations and the concentration dependence of neural excitation. Pestic Biochem Physiol 60:103–110

    Article  Google Scholar 

  • Sattelle DB (1986) Insect acetylcholine receptors—biochemical and physiological approaches. In: Neuropharmacology and pesticide action, vol 144. Ellis Horwood Limited VCH, Chichester and Weinheim, pp 445–497

  • Sattelle DB (1990) γ-Aminobutyric acid receptors of insects. Adv Insect Physiol 22:1–113

    Google Scholar 

  • Sattelle DB, Yamamoto D (1988) Molecular targets of pyrethroid insecticides. Adv Insect Physiol 20:147–213

    Google Scholar 

  • Sattelle DB, Harrow ID, David JA, Pelhate M, Callec JJ, Gepner JI, Hall LM (1985) Nereistoxin: actions on an acetylcholine receptor/ion channel complex in the central nervous system of an insect Periplaneta americana (L.). J Exp Biol 118:37–52

    Google Scholar 

  • Sattelle DB, Culetto E, Grauso M, Raymond V, Franks C, Towers P (2002) Functional genomics of ionotropic acetylcholine receptors in Caenorhabditis elegans and Drosophila melanogaster. In: Ion channels: from atomic physiology to functional genomics (Novartis symposium 245). Wiley, UK, pp 240–260

  • Sattelle DB, Jones AK, Sattelle BM, Matsuda K, Reenan R, Biggin PC (2005) Edit, cut and paste in the nicotinic acetylcholine receptor gene family of Drosophila melanogaster. Bioessays 27:366–376

    Article  Google Scholar 

  • Schaeffer JM, Haines HW (1989) Avermectin binding in Caenorhabditis elegans. A two-state model for the avermectin binding site. Biochem Pharmacol 38:2329–2338

    Article  Google Scholar 

  • Semenov EP, Pak WL (1999) Diversification of Drosophila chloride channel gene by multiple posttranscriptional mRNA modifications. J Neurochem 72:66–72

    Article  Google Scholar 

  • Shimomura M, Okuda H, Matsuda K, Komai K, Akamatsu M, Sattelle DB (2002) Effects of mutations of a glutamine residue in loop D of the α 7 nicotinic acetylcholine receptor on agonist profiles for neonicotinoid insecticides and related ligands. Br J Pharmacol 137:162–169

    Article  Google Scholar 

  • Sigel E, Baur R (1987) Effect of avermectin B1a on chick neuronal γ-aminobutyrate receptor channels expressed in Xenopus oocytes. Mol Pharmacol 32:749–752

    PubMed  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(3):126–136

    Article  Google Scholar 

  • Smith McHM, Warren VA, Thomas BS, Broch RM, Ertel EA, Rohrer S, Schaeffer J et al (2000) Nodulisporic acid opens insect glutamate-gated chloride channels: identification of a new high affinity modulator. Biochemistry 39:5543–5554

    Article  Google Scholar 

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

    Article  Google Scholar 

  • Sparks TC, Kirst HA, Mynderse JS, Thompson GD, Turner JR, Jantz O, Hertlein MB et al (1996) Chemistry and Biology of the spinosyns: components of spinosad (Tracer), the first entry into Dow Elanco’s naturalyte class of insect control products. Proc Beltwide Cotton Conf 2:692–696

    Google Scholar 

  • Tan J, Liu Z, Nomura Y, Goldin AL, Dong K (2002a) Alternative splicing of an insect sodium channel gene generates pharmacologically distinct sodium channels. J Neurosci 22:5300–5309

    Google Scholar 

  • Tan J, Liu Z, Tsai TD, Valles SM, Goldin AL, Dong K (2002b) Novel sodium channel gene mutations in Blattella germanica reduce the sensitivity of expressed channels to deltamethrin. Insect Biochem Mol Biol 32:445–454

    Article  Google Scholar 

  • 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  Google Scholar 

  • Towers PR, Sattelle DB (2002) A Drosophila melanogaster cell line (S2) facilitates post-genome functional analysis of receptors and ion channels. Bioessays 24:1066–1073

    Article  Google Scholar 

  • Unwin N (1993) Nicotinic acetylcholine receptor at 9 A resolution. J Mol Biol 299:1101–1124

    Article  Google Scholar 

  • Warmke JW, Reenan RA, Wang P, Qian S, Arena JP, Wang J, Wunderler D, Liu K, Kaczorowski GI, Van der Ploeg LH, Ganetzky B, Cohen CJ (1997) Functional expression of Drosophila para sodium channels. Modulation by the membrane protein TipE and toxin pharmacology. J Gen Physiol 110:119–133

    Article  Google Scholar 

  • Watson GB (2001) Actions of insecticidal spinosyns on γ-aminobutyric acid responses from small-diameter cockroach neurons. Pest Biochem Physiol 71:20–28

    Article  Google Scholar 

  • Williamson MS, Denholm I, Bell CA, Devonshire AL (1993) Knockdown resistance (kdr) to DDT and pyrethroid insecticides maps to a sodium channel gene locus in the housefly (Musca domestica). Mol Gen Genet 240:17–22

    Article  Google Scholar 

  • Williamson MS, Martinez-Torres D, Hick CA, Devonshire AL (1996) Identification of mutations in the housefly para-type sodium channel gene associated with knockdown resistance (kdr) to pyrethroid insecticides. Mol Gen Genet 252:51–60

    Article  Google Scholar 

  • Wing KD, Schnee ME, Sacher M, Connair M (1998) A novel oxadiazine insecticide is bioactived in lepidopteran larvae. Arch Insect Biochem Physiol 37:91–103

    Article  Google Scholar 

  • Wolff MA, Wingate VP (1998) Characterization and comparative pharmacological studies of a functional gamma-aminobutyric acid (GABA) receptor cloned from the tobacco budworm, Heliothis virescens (Noctuidae: Lepidoptera). Invert Neurosci 3:305–315

    PubMed  Google Scholar 

  • Yu FH, Catterall WA (2003) Overview of the voltage-gated sodium channel family. Genome Biol 4:207.1–207.7

    Article  Google Scholar 

  • Zhao X, Nagata K, Marszalec W, Yeh JZ, Narahashi T (1999) Effects of the oxadiazine insecticide Indoxacarb (DPX-MP062) on neuronal nicotinic acetylcholine receptors in mammalian neurons. Neurotoxicology 20:561–570

    PubMed  Google Scholar 

  • Zhao X, Yeh JZ, Salgado VL, Narahashi T (2004) Fipronil is a potent open channel blocker of glutamate-activated chloride channels in cockroach neurons. J Pharm Exp Ther 310:192–201

    Article  Google Scholar 

  • Zlotkin E (1999) The insect-voltage gated sodium channel as target of insecticides. Annu Rev Entomol 44:429–455

    Article  Google Scholar 

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Acknowledgement

The authors thank Jeff Bloomquist, Daniel Cordova and Steven Buckingham for helpful discussions and comments on an earlier draft of the manuscript.

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Correspondence to David B. Sattelle.

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Raymond-Delpech, V., Matsuda, K., Sattelle, B.M. et al. Ion channels: molecular targets of neuroactive insecticides. Invert Neurosci 5, 119–133 (2005). https://doi.org/10.1007/s10158-005-0004-9

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Keywords

  • Molecular targets of insecticides
  • Sodium channels
  • Ionotropic receptors
  • Resistance genes