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1.  Differential State-Dependent Modification of Rat Nav1.6 Sodium Channels Expressed in Human Embryonic Kidney (HEK293) Cells by the Pyrethroid Insecticides Tefluthrin and Deltamethrin 
Toxicology and applied pharmacology  2011;257(3):377-387.
We expressed rat Nav1.6 sodium channels in combination with the rat β1 and β2 auxiliary subunits in human embryonic kidney (HEK293) cells and evaluated the effects of the pyrethroid insecticides tefluthrin and deltamethrin on expressed sodium currents using the whole-cell patch clamp technique. Both pyrethroids produced concentration-dependent, resting modification of Nav1.6 channels, prolonging the kinetics of channel inactivation and deactivation to produce persistent “late” currents during depolarization and tail currents following repolarization. Both pyrethroids also produced concentration dependent hyperpolarizing shifts in the voltage dependence of channel activation and steady-state inactivation. Maximal shifts in activation, determined from the voltage dependence of the pyrethroid-induced late and tail currents, were ~25 mV for tefluthrin and ~20 mV for deltamethrin. The highest attainable concentrations of these compounds also caused shifts of ~5–10 mV in the voltage dependence of steady-state inactivation. In addition to their effects on the voltage dependence of inactivation, both compounds caused concentration-dependent increases in the fraction of sodium current that was resistant to inactivation following strong depolarizing prepulses. We assessed the use-dependent effects of tefluthrin and deltamethrin on Nav1.6 channels by determining the effect of trains of 1 to 100 5-ms depolarizing prepulses at frequencies of 20 or 66.7 Hz on the extent of channel modification. Repetitive depolarization at either frequency increased modification by deltamethrin by ~2.3-fold but had no effect on modification by tefluthrin. Tefluthrin and deltamethrin were equally potent as modifiers of Nav1.6 channels in HEK293 cells using the conditions producing maximal modification as the basis for comparison. These findings show that the actions of tefluthrin and deltamethrin of Nav1.6 channels in HEK293 cells differ from the effects of these compounds on Nav1.6 channels in Xenopus oocytes and more closely reflect the actions of pyrethroids on channels in their native neuronal environment.
PMCID: PMC3226847  PMID: 21983428
voltage-gated sodium channel; Nav1.6 isoform; pyrethroid; deltamethrin; tefluthrin; HEK293 cells
2.  Coexpression with Auxiliary β Subunits Modulates the Action of Tefluthrin on Rat Nav1.6 and Nav1.3 Sodium Channels 
We expressed the rat Nav1.3 and Nav1.6 sodium channel α subunit isoforms in Xenopus oocytes either alone or with the rat β1 and β2 auxiliary subunits in various combinations and assessed the sensitivity of the expressed channels to resting and use-dependent modification by the pyrethroid insecticide tefluthrin using the two-electrode voltage clamp technique. Coexpression with the β1 and β2 subunits, either individually or in combination, did not affecting the resting sensitivity of Nav1.6 channels to tefluthrin. Modification by tefluthrin of Nav1.6 channels in the absence of β subunits was not altered by the application of trains of high-frequency depolarizing prepulses. By contrast, coexpression of the Nav1.6 channel with the β1 subunit enhanced the extent of channel modification twofold following repeated depolarization. Coexpression of Nav1.6 with the β2 subunit also slightly enhanced modification following repeated depolarization, but coexpression of Nav1.6 with both β subunits caused enhanced modification following repeated depolarization that was indistinguishable from that found with Nav1.6+β1 channels. In contrast to Nav1.6, the resting modification by tefluthrin of Nav1.3 channels expressed in the absence of β subunits was reduced by repeated depolarization. However, tefluthrin modification of the Nav1.3 α subunit expressed with both β subunits was enhanced 1.7-fold by repeated depolarization, thereby confirming that β subunit modulation of use-dependent effects was not confined to the Nav1.6 isoform. These results show that the actions of pyrethroids on mammalian sodium channels in the Xenopus oocyte expression system are determined in part by the interactions of the sodium channel α subunit with the auxiliary β subunits that are part of the heteromultimeric sodium channel complexes found in neurons and other excitable cells.
PMCID: PMC3346283  PMID: 22577241
voltage-gated sodium channels; Nav1.6 isoform; Nav1.3 isoform; β subunit; voltage clamp; tefluthrin
3.  Indoxacarb, Metaflumizone, and Other Sodium Channel Inhibitor Insecticides: Mechanism and Site of Action on Mammalian Voltage-Gated Sodium Channels 
Sodium channel inhibitor (SCI) insecticides were discovered almost four decades ago but have only recently yielded important commercial products (eg., indoxacarb and metaflumizone). SCI insecticides inhibit sodium channel function by binding selectively to slow-inactivated (non-conducting) sodium channel states. Characterization of the action of SCI insecticides on mammalian sodium channels using both biochemical and electrophysiological approaches demonstrates that they bind at or near a drug receptor site, the "local anesthetic (LA) receptor." This mechanism and site of action on sodium channels differentiates SCI insecticides from other insecticidal agents that act on sodium channels. However, SCI insecticides share a common mode of action with drugs currently under investigation as anticonvulsants and treatments for neuropathic pain. In this paper we summarize the development of the SCI insecticide class and the evidence that this structurally diverse group of compounds have a common mode of action on sodium channels. We then review research that has used site-directed mutagenesis and heterologous expression of cloned mammalian sodium channels in Xenopus laevis oocytes to further elucidate the site and mechanism of action of SCI insecticides. The results of these studies provide new insight into the mechanism of action of SCI insecticides on voltage-gated sodium channels, the location of the SCI insecticide receptor, and its relationship to the LA receptor that binds therapeutic SCI agents.
PMCID: PMC3780446  PMID: 24072940
indoxacarb; DCJW; metaflumizone; RH3421; sodium channel; local anesthetic receptor
4.  Actions of Tefluthrin on Rat Nav1.7 Voltage-Gated Sodium Channels Expressed in Xenopus Oocytes 
In rats expression of the Nav1.7 voltage-gated sodium channel isoform is restricted to the peripheral nervous system and is abundant in the sensory neurons of the dorsal root ganglion. We expressed the rat Nav1.7 sodium channel α subunit together with the rat auxiliary β1 and β2 subunits in Xenopus laevis oocytes and assessed the effects of the pyrethroid insecticide tefluthrin on the expressed currents using the two-electrode voltage clamp method. Tefluthrin at 100 µM modified of Nav1.7 channels to prolong inactivation of the peak current during a depolarizing pulse, resulting in a marked "late current" at the end of a 40-ms depolarization, and induced a sodium tail current following repolarization. Tefluthrin modification was enhanced up to two-fold by the application of a train of up to 100 5-ms depolarizing prepulses. These effects of tefluthrin on Nav1.7 channels were qualitatively similar to its effects on rat Nav1.2, Nav1.3 and Nav1.6 channels assayed previously under identical conditions. However, Nav1.7 sodium channels were distinguished by their low sensitivity to modification by tefluthrin, especially compared to Nav1.3 and Nav1.6 channels. It is likely that Nav1.7 channels contribute significantly to the tetrodotoxin-sensitive, pyrethroid-resistant current found in cultured dorsal root ganglion neurons. We aligned the complete amino acid sequences of four pyrethroid-sensitive isoforms (house fly Vssc1; rat Nav1.3, Nav1.6 and Nav1.8) and two pyrethroid-resistant isoforms (rat Nav1.2 and Nav1.7) and found only a single site, located in transmembrane segment 6 of homology domain I, at which the amino acid sequence was conserved among all four sensitive isoform sequences but differed in the two resistant isoform sequences. This position, corresponding to Val410 of the house fly Vssc1 sequence, also aligns with sites of multiple amino acid substitutions identified in the sodium channel sequences of pyrethroid-resistant insect populations. These results implicate this single amino acid polymorphism in transmembrane segment 6 of sodium channel homology domain I as a determinant of the differential pyrethroid sensitivity of rat sodium channel isoforms.
PMCID: PMC3181098  PMID: 21966053
voltage-gated sodium channel; Nav1.7 isoform; pyrethroid; tefluthrin; peripheral nervous system; dorsal root ganglion
5.  Divergent Actions of the Pyrethroid Insecticides S-Bioallethrin, Tefluthrin and Deltamethrin on Rat Nav1.6 Sodium Channels 
Toxicology and applied pharmacology  2010;247(3):229-237.
We expressed rat Nav1.6 sodium channels in combination with the rat β1 and β2 auxiliary subunits in Xenopus laevis oocytes and evaluated the effects of the pyrethroid insecticides S-bioallethrin, deltamethrin and tefluthrin on expressed sodium currents using the two-electrode voltage clamp technique. S-Bioallethrin, a Type I structure, produced transient modification evident in the induction of rapidly-decaying sodium tail currents, weak resting modification (5.7% modification at 100 μM), and no further enhancement of modification upon repetitive activation by high-frequency trains of depolarizing pulses. By contrast deltamethrin, a Type II structure, produced sodium tail currents that were ~9-fold more persistent than those caused by S-bioallethrin, barely detectable resting modification (2.5% modification at 100 μM), and 3.7-fold enhancement of modification upon repetitive activation. Tefluthrin, a Type I structure with high mammalian toxicity, exhibited properties intermediate between S-bioallethrin and deltamethrin: intermediate tail current decay kinetics, much greater resting modification (14.1% at 100 μM), and 2.8-fold enhancement of resting modification upon repetitive activation. Comparison of concentration–effect data showed that repetitive depolarization increased the potency of tefluthrin ~15-fold and that tefluthrin was ~10-fold more potent than deltamethrin as a use-dependent modifier of Nav1.6 sodium channels. Concentration–effect data from parallel experiments with the rat Nav1.2 sodium channel co-expressed with the rat β1 and β2 subunits in oocytes showed that the Nav1.6 isoform was at least 15-fold more sensitive to tefluthrin and deltamethrin than the Nav1.2 isoform. These results implicate sodium channels containing the Nav1.6 isoform as potential targets for the central neurotoxic effects of pyrethroids.
PMCID: PMC2929565  PMID: 20624410
voltage-gated sodium channel; Nav1.6 isoform; pyrethroid; S-bioallethrin; deltamethrin; tefluthrin
6.  Functional Expression of Rat Nav1.6 Voltage-Gated Sodium Channels in HEK293 Cells: Modulation by the Auxiliary β1 Subunit 
PLoS ONE  2014;9(1):e85188.
The Nav1.6 voltage-gated sodium channel α subunit isoform is abundantly expressed in the adult rat brain. To assess the functional modulation of Nav1.6 channels by the auxiliary β1 subunit we expressed the rat Nav1.6 sodium channel α subunit by stable transformation in HEK293 cells either alone or in combination with the rat β1 subunit and assessed the properties of the reconstituted channels by recording sodium currents using the whole-cell patch clamp technique. Coexpression with the β1 subunit accelerated the inactivation of sodium currents and shifted the voltage dependence of channel activation and steady-state fast inactivation by approximately 5–7 mV in the direction of depolarization. By contrast the β1 subunit had no effect on the stability of sodium currents following repeated depolarizations at high frequencies. Our results define modulatory effects of the β1 subunit on the properties of rat Nav1.6-mediated sodium currents reconstituted in HEK293 cells that differ from effects measured previously in the Xenopus oocyte expression system. We also identify differences in the kinetic and gating properties of the rat Nav1.6 channel expressed in the absence of the β1 subunit compared to the properties of the orthologous mouse and human channels expressed in this system.
PMCID: PMC3880341  PMID: 24404202
7.  Compound-Specific Effects of Mutations at Val787 in DII-S6 of Nav1.4 Sodium Channels on the Action of Sodium Channel Inhibitor Insecticides 
Neurotoxicology  2012;33(5):1381-1389.
Sodium channel inhibitor (SCI) insecticides are hypothesized to inhibit voltage-gated sodium channels by binding selectively to the slow-inactivated state. Replacement of valine at position 787 in the S6 segment of homology domain II of the rat Nav1.4 sodium channel by lysine (V787K) enchances slow inactivation of this channel whereas replacement by alanine or cysteine (V787A, V787C) inhibits slow inactivation. To test the hypothesis that SCI insecticides bind selectively to the slow-inactivated state, we constructed mutated Nav1.4/V787A, Nav1.4/V787C, and Nav1.4/V787K cDNAs, expressed wildtype and mutated channels with the auxiliary β1 subunit in Xenopus oocytes, and used the two-electrode voltage clamp technique to examine the effects of these mutations on channel inhibition by four SCI insecticides (indoxacarb, its bioactivated metabolite DCJW, metaflumizone, and RH3421). Mutations at Val787 affected SCI insecticide sensitivity in a manner that was independent of mutation-induced changes in slow inactivation gating. Sensitivity to inhibition by 10 μM indoxacarb was significantly increased in all three mutated channels, whereas sensitivity to inhibition by 10 μM metaflumizone was significantly reduced in Nav1.4/V787A channels and completely abolished in Nav1.4/V787K channels. The effects of Val787 mutations on metaflumizone were correlated with the hydrophobicity of the substituted amino acid rather than the extent of slow inactivation. None of the mutations at Val787 significantly affected the sensitivity to inhibition by DCJW or RH3421. These results demonstrate that the impact of mutations at Val787 on sodium channel inhibition by SCI insecticides depends on the specific insecticide examined and is independent of mutation-induced changes in slow inactivation gating. We propose that Val787 may be a unique determinant of metaflumizone binding.
PMCID: PMC3484372  PMID: 22983119
Sodium channel; inhibition; insecticide; slow inactivation; indoxacarb; metaflumizone
8.  Human and Rat Nav1.3 Voltage-Gated Sodium Channels Differ in Inactivation Properties and Sensitivity to the Pyrethroid Insecticide Tefluthrin 
Neurotoxicology  2008;30(1):81-89.
Voltage-gated sodium channels are important sites for the neurotoxic actions of pyrethroid insecticides in mammals. The pore-forming α subunits of mammalian sodium channels are encoded by a family of 9 genes, designated Nav1.1 - Nav1.9. Native sodium channels in the adult central nervous system (CNS) are heterotrimeric complexes of one of these 9 α subunits and two auxiliary (β) subunits. Here we compare the functional properties and pyrethroid sensitivity of the rat and human Nav1.3 isoforms, which are abundantly expressed in the developing CNS. Coexpression of the rat Nav1.3 and human Nav1.3 α subunits in combination with their conspecific β1 and β2 subunits in Xenopus laevis oocytes gave channels with markedly different inactivation properties and sensitivities to the pyrethroid insecticide tefluthrin. Rat Nav1.3 channels inactivated more slowly than human Nav1.3 channels during a depolarizing pulse. The rat and human channels also differed in their voltage dependence of steady-state inactivation. Exposure of rat and human Nav1.3 channels to 100 μM tefluthrin in the resting state produced populations of channels that activated, inactivated and deactivated more slowly than unmodified channels. For both rat and human channels, application of trains of depolarizing prepulses enhanced the extent of tefluthrin modification approximately twofold; this result implies that tefluthrin may bind to both the resting and open states of the channel. Modification of rat Nav1.3 channels by 100 μM tefluthrin was four-fold greater than that measured in parallel assays with human Nav1.3 channels. Human Nav1.3 channels were also less sensitive to tefluthrin than rat Nav1.2 channels, which are considered to be relatively insensitive to pyrethroids. These data provide the first direct comparison of the functional and pharmacological properties of orthologous rat and human sodium channels and demonstrate that orthologous channels with a high degree of amino acid sequence conservation differ in both their functional properties and their sensitivities to pyrethroid insecticides.
PMCID: PMC2696113  PMID: 19026681
Nav1.3; oocyte; sodium channel; pyrethroid; tefluthrin; rat; human
9.  Differential state-dependent modification of inactivation-deficient Nav1.6 sodium channels by the pyrethroid insecticides S-bioallethrin, tefluthrin and deltamethrin 
Neurotoxicology  2012;33(3):384-390.
Pyrethroid insecticides disrupt nerve function by modifying the gating kinetics of transitions between the conducting and nonconducting states of voltage-gated sodium channels. Pyrethroids modify rat Nav1.6 + β1 + β2 channels expressed in Xenopus oocytes in both the resting state and in one or more states that require channel activation by repeated depolarization. The state dependence of modification depends on the pyrethroid examined: deltamethrin modification requires repeated channel activation, tefluthrin modification is significantly enhanced by repeated channel activation, and S-bioallethrin modification is unaffected by repeated activation. Use-dependent modification by deltamethrin and tefluthrin implies that these compounds bind preferentially to open channels. We constructed the rat Nav1.6Q3 cDNA, which contained the IFM/QQQ mutation in the inactivation gate domain that prevents fast inactivation and results in a persistently open channel. We expressed Nav1.6Q3 + β1 + β2 sodium channels in Xenopus oocytes and assessed the modification of open channels by pyrethroids by determining the effect of depolarizing pulse length on the normalized conductance of the pyrethroid-induced sodium tail current. Deltamethrin caused little modification of Nav1.6Q3 following short (10 ms) depolarizations, but prolonged depolarizations (up to 150 ms) caused a progressive increase in channel modification measured as an increase in the conductance of the pyrethroid-induced sodium tail current. Modification by tefluthrin was clearly detectable following short depolarizations and was increased by long depolarizations. By contrast modification by S-bioallethrin following short depolarizations was not altered by prolonged depolarization. These studies provide direct evidence for the preferential binding of deltamethrin and tefluthrin (but not S-bioallethrin) to Nav1.6Q3 channels in the open state and imply that the pyrethroid receptor of resting and open channels occupies different conformations that exhibit distinct structure–activity relationships.
PMCID: PMC3574822  PMID: 22465659
Sodium channel; Nav1.6; Use-dependent modification; Deltamethrin; S-bioallethrin; Tefluthrin
10.  Molecular Mechanisms of Pyrethroid Insecticide Neurotoxicity: Recent Advances 
Archives of Toxicology  2011;86(2):165-181.
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.
PMCID: PMC3218237  PMID: 21710279
pyrethroid; insecticide; neurotoxicity; voltage-gated sodium channel; voltage-gated calcium channel; voltage-gated chloride channel
11.  Independent and Joint Modulation of Rat Nav1.6 Voltage-Gated Sodium Channels by Coexpression with the Auxiliary β1 and β2 Subunits 
The Nav1.6 voltage-gated sodium channel α subunit isoform is the most abundant isoform in the brain and is implicated in the transmission of high frequency action potentials. Purification and immunocytochemical studies imply that Nav1.6 exist predominantly as Nav1.6+β1+β2 heterotrimeric complexes. We assessed the independent and joint effects of the rat β1 and β2 subunits on the gating and kinetic properties of rat Nav1.6 channels by recording whole-cell currents in the two-electrode voltage clamp configuration following transient expression in Xenopus oocytes. The β1 subunit accelerated fast inactivation of sodium currents but had no effect on the voltage dependence of their activation and steady-state inactivation and also prevented the decline of currents following trains of high-frequency depolarizing prepulses. The β2 subunit selectively retarded the fast phase of fast inactivation and shifted the voltage dependence of activation towards depolarization without affecting other gating properties and had no effect on the decline of currents following repeated depolarization. The β1 and β2 subunits expressed together accelerated both kinetic phases of fast inactivation, shifted the voltage dependence of activation towards hyperpolarization, and gave currents with a persistent component typical of those recorded from neurons expressing Nav1.6 sodium channels. These results identify unique effects of the β1 and β2 subunits and demonstrate that joint modulation by both auxiliary subunits gives channel properties that are not predicted by the effects of individual subunits.
PMCID: PMC3082003  PMID: 21439942
voltage-gated sodium channels; Nav1.6; β subunits; voltage clamp; kinetics; steady-state properties
12.  State-Dependent Modification of Voltage-Gated Sodium Channels by Pyrethroids 
Pyrethroids disrupt nerve function by altering the rapid kinetic transitions between conducting and nonconducting states of voltage-gated sodium channels that underlie the generation of nerve action potentials. Recent studies of pyrethroid action on cloned insect and mammalian sodium channel isoforms expressed in Xenopus laevis oocytes show that in some cases pyrethroid modification is either absolutely dependent on or significantly enhanced by repeated channel activation. These use-dependent effects have been interpreted as evidence of preferential binding of at least some pyrethroids to the open, rather than resting, state of the sodium channel. This paper reviews the evidence for state-dependent modification of insect and mammalian sodium channels expressed in oocytes by pyrethroids and considers the implications of state-dependent effects for understanding the molecular mechanism of pyrethroid action and the development and testing of models of the pyrethroid receptor.
PMCID: PMC2905833  PMID: 20652092
pyrethroid; cismethrin; cypermethrin; deltamethrin; permethrin; tefluthrin; sodium channel; insect; rat; human
13.  Human Embryonic Kidney (HEK293) Cells Express Endogenous Voltage-Gated Sodium Currents and Nav1.7 Sodium Channels 
Neuroscience letters  2009;469(2):268.
Human embryonic kidney (HEK293) cells are widely used for the heterologous expression of voltage- and ligand-gated ion channels. Patch clamp analysis of HEK293 cells in the whole-cell configuration identified voltage-gated, rapidly inactivating inward currents. Peak current amplitudes ranged from less than 100 pA to more than 800 pA, with the majority (84 of 130 cells) in the 100–400 pA range. Transient inward currents were separated into three components on the basis of sensitivity to cadmium and tetrodotoxin (TTX). Application of cadmium (300 μM) reduced current amplitude to 65% of control, consistent with the existence of current carried by a cadmium -sensitive nonspecific cation channel previously identified in HEK293 cells. Application of TTX (500 nM) reduced current amplitude by 47%, consistent with the existence of current carried by a TTX-sensitive voltage-gated sodium channel. Joint application of cadmium and TTX was additive, reducing current amplitude to 28% of control. The residual cadmium- and TTX-resistant current represents a third pharmacologically distinct component of the rapidly inactivating inward current that was not characterized further. The pyrethroid insecticide tefluthrin (10 μM) prolonged the inactivation of transient currents and induced slowly decaying tail currents, effects that are characteristic of sodium channel modification by pyrethroids. The use of sodium channel isoform-specific primers in polymerase chain reaction amplifications on HEK293 cell first-strand cDNA detected the consistent expression of the human Nav1.7 sodium channel isoform in cells that expressed the TTX-sensitive component of current. These results provide evidence for an endogenous TTX-sensitive sodium current in HEK293 cells that is associated primarily with the expression of the Nav1.7 sodium channel isoform.
PMCID: PMC2815232  PMID: 20006571
HEK293 cells; sodium channels; Nav1.7; tetrodotoxin; tefluthrin
14.  Three mutations identified in the voltage-sensitive sodium channel α-subunit gene of permethrin-resistant human head lice reduce the permethrin sensitivity of house fly Vssc1 sodium channels expressed in Xenopus oocytes 
Point mutations in the para-orthologous sodium channel α-subunit of the head louse (M815I, T917I and L920F) are associated with permethrin- and DDT-resistance. These mutations were inserted in all combinations using site-directed mutagenesis at the corresponding amino acid sequence positions (M827I, T929I and L932F) of the house fly para-orthologous voltage-sensitive sodium channel α-subunit (Vssc1WT) gene and heterologously co-expressed with the sodium channel auxiliary subunit of house fly (Vsscβ) in Xenopus oocytes. The double mutant possessing M827I and T929I (Vssc1MITI/Vsscβ) caused a ~4.0 mV hyperpolarizing shift and the triple mutant, Vssc1MITILF/Vsscβ, caused a ~3.2 mV depolarizing shift in the voltage dependence of activation curves. Vssc1MITI/Vsscβ, Vssc1TILF/Vsscβ and Vssc1MITILF/Vsscβ caused depolarizing shifts (~6.6, ~7.6 and ~8.8 mV, respectively) in the voltage dependence of steady-state inactivation curves. The M827I and L932F mutations reduced permethrin sensitivity when expressed alone but the T929I mutation, either alone or in combination, virtually abolished permethrin sensitivity. Thus, the T929I mutation is the principal cause of permethrin resistance in head lice. Comparison of the expression rates of channels containing single, double and triple mutations with that of Vssc1WT/Vsscβ channels indicates that the M827I mutation may play a role in rescuing the decreased expression of channels containing T929I.
PMCID: PMC2329913  PMID: 18252244
Heterologous expression; Human head lice; Knockdown resistance; Pediculus humanus capitis; Permethrin resistance; Voltage-sensitive sodium channel

Results 1-14 (14)