Sodium channels pyrethroids

New agrochemicals introduced in the past five years include new chemistries with known modes of action, such as the protoporphyrinogen inhibitor bencarba-zone, the phytoene desaturase picolinafen and beflutamid, and sodium channel pyrethroids new chemistries with possibly new modes of action, such as flonic-amid and pyridalyl and new chemistries with established new modes of actions, such as flubendiamide, which activates ryanodine-sensitive intracellular calcium release channels, ryanodine receptors RyR, in insects. 

The compounds featured in Table 1.1 are considered briefly here. Pyrethrins are lipophilic esters that occur in Chrysanthemum spp. Extracts of flower heads of Chrysanthemum spp. contain six different pyrethrins and have been used for insect control (Chapter 12). Pyrethrins act upon sodium channels in a manner similar to p,p -DDT. The highly successful synthetic pyrethroid insecticides were modeled on natural pyrethrins. 

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). 

Pyrethroid insecticides are generally recognized as potent neurotoxicants that interfere with nerve membrane function by interaction with the sodium channel (Elliott and Janes 1978 Vijverberg et al. 1982 Gilbert et al. 1989 Haya 1989). Synthetic pyrethroids are more toxic against insect pests, up to 10 times more potent in some cases, than other insecticides now in general use (Bradbury... 

Induction of repetitive activity in the nervous system is the principal effect of pyrethroids. Repetitive activity originates from a prolongation of the transient increase in sodium permeability of the nerve membrane associated with excitation. All pyrethroids affect sodium channel gating in a similar manner, although Type II pyrethroids are significantly more neurotoxic than Type I pyrethroids. 

The sodium channel in the nerve membrane is the major target site for all synthetic pyrethroid insecticides (and many other neurotoxicants)... 

Salgado, V.L., M.D. Herman, and T. Narahashi. 1989. Interactions of the pyrethroid fenvalerate with nerve membrane sodium channels temperature dependence and mechanism of depolarization. Neurotoxicology 10 1-14. 

Keywords CS-syndrome Neurotransmitter release Pyrethroids T-syndrome Voltage-gated calcium channels Voltage-gated sodium channels... 

There have been many studies over the last 40 years that provide substantial evidence that voltage-gated sodium channels in the CNS are major sites of action for the pyrethroids in mammals [1, 20-25]. This literature has been recently critically reviewed by Soderlund [10] from the viewpoint of the neurotoxic action of pyrethroids in mammals and we will rely heavily on this review in our summary below. 

Using both voltage- and patch-clamp electrophysiological protocols, pyrethroids have been shown to affect the kinetic properties of voltage-gated sodium channels in a way that is consistent with their neuroexcitability [22], With voltage-clamp,... 

This problem of overlapping expression of sodium channel isoforms has recently begun to be addressed using cloned channels heterologously expressed individually in Xenopus laevis oocytes with voltage-clamp techniques and the picture that is emerging is that there are substantial differences in the sensitivity of mammalian sodium channel isoforms to the pyrethroids. 

Recent results that examined the effect of pyrethroids on voltage-gated sodium channels expressed in human embryonic kidney (HEK293) cells grown in... 

The Pyrethroid Receptor on Sodium Channels and Implications of the State-Dependent Actions of Pyrethroids... 

A main consideration in modeling the pyrethroid receptor on insect sodium channels in the open state was the determination that channel modification by cypermethrin and deltamethrin of cloned insect sodium channels expressed in Xenopus oocytes occurred only following repeated depolarizations [33, 55]. This use-dependency of some pyrethroids was the basis for the widely held opinion that these pyrethroids bind preferentially to open sodium channels and that state-dependent modification of sodium channels by pyrethroids was an important consideration for any receptor modeling. 

Neurotransmitter release induced by potassium-dependent depolarization is a physiologically relevant way to investigate pyrethroid effects on calcium-dependent neurotransmitter release since this process is independent of voltage-sensitive sodium channels [71]. Furthermore, potassium-stimulated calcium influx and subsequent neurotransmitter release by synaptosomes is blocked by a variety of voltage-sensitive calcium channel antagonists but not by TTX [4, 71, 72]. 

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