Sodium channels pyrethroid resistance

In some resistant strains, both types of resistance mechanism have been shown to operate against the same insecticide. Thus, the PEG87 strain of the tobacco bud worm (Heliothis virescens) is resistant to pyrethroids on account of both a highly active form of cytochrome P450 and an insensitive form of the sodium channel (Table 4.3 and McCaffery 1998). 

Song JH, Narahashi T (1996) Differential effects of the pyrethroid tetramethrin on tetrodotoxin-sensitive and tetrodotoxin-resistant single sodium channels. Brain Res 712 258-264... 

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... 

Lee SH, Soderlund DM (2001) The V410M 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... 

He, H., Chen, A.C., Davey, R.B., Ivie, G.W., and George, J.E., Identification of a point mutation in the para-type sodium channel gene from a pyrethroid resistant cattle tick, Biochem. Biophys. Res. Commun., 261, 558,1999. 

Morin, S., Williamson, M.S., Goodson, S.J., Brown, J.K., Tabashnik, B.E., and Dennehy, T.J., Mutations in the Bacillus tabaci para sodium channel gene associated with resistance to a pyrethroid plus organophosphorus mixture, Insect Biochem. Molec. Biol., 32,1781, 2002. 

Roditakis, E., Tsagkarakou, A., and Vontas, J., Identification of mutations in the para sodium channel of Bemisia tabaci from Crete, associated with resistance to pyrethroids, Pestic. Biochem. Physiol., 85,161, 2006. 

Pyrethroids are widely used to control many agriculturally and medically important insect pests. Due to intensive use of pyrethroids in pest control, many pest populations have developed resistance to these compounds. One major mechanism of pyrethroid resistance, conferred by the knock down resistance gene (Mr), is reduced target site (sodium channel) sensitivity to DDT and pyrethroids. Studies on the molecular basis of Mr and Mr-type resistance in various insects are enhancing our understanding of the structure and function of insect sodium channels and the molecular interaction between insect sodium channels and pyrethroids. In this chapter, I will review recent advances in... 

Because of the intimate involvement of sodium channels in pyrethroid insecticide resistance (see below), partial cDNA clones of para-orthologs were isolated from other in-... 

Naturally Occurring Point Mutations in the Sodium Channel Gene Responsible for Knockdown Resistance to Pyrethroids. 

Several point mutations in the sodium channel gene are associated with kdr and kdr-type resistance to pyrethroids in agriculturally or medically important arthropod species. The most common mutation is the leucine (L) to phenylalanine (F) or histidine (H) or serine... 

Different forms of the sodium channel show differential sensitivity to pyrethroids. Pyrethroids are 10 times more potent on the tetrodotoxin-resistant subtype of the sodium channel, which is expressed in the developing mammalian brain and in adult dorsal root ganglia. The different forms can show structure-specific sensitivity also the rat brain Ila form being sensitive to type II, but not type I pyrethroids. Some of the selectivity of action of pyrethroids within the nervous system parallels the distribution of sensitive sodium channel subtypes, although there are at present only limited data to support this. Peripheral nerve (SNS/PN3) sodium channels are highly sensitive to pyrethroids, and action at these channels may be relevant to the production of paresthesia. 

The action of deltamethrin on the GABA response was more difficult to determine, because low concentrations of deltamethrin caused depolarization and rapid firing of action potentials, accompanied by a decrease in membrane resistance. Deltamethrin at 0.1 nM caused a massive increase in firing frequency, and a depolarization of 30mV, after perfusion for ten minutes. Application of TTX, which specifically blocks voltage dependent sodium channels, abolished the action potentials, and also reversed the pyrethroid-induced depolarization and decrease in membrane resistance. 

The target biomolecules for DDT and the pyrethroids are the sodium channels in the axon. One very common type of resistance is the so-called knockdown resistance, or kdr resistance. In this case one or more amino acids have been changed due to point mutation so that DDT or pyrethroids do not bind. Whereas houseflies that are resistant due to the presence of the DDT dehydrochlorinase type of glutathione transferase will be paralyzed by DDT, it is found that when DDT has been detoxicated, the flies wake up and... 

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