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Neurotoxicology
2009 Jan 01;301:81-9. doi: 10.1016/j.neuro.2008.10.008.
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Human and rat Nav1.3 voltage-gated sodium channels differ in inactivation properties and sensitivity to the pyrethroid insecticide tefluthrin.
Tan J
,
Soderlund DM
.
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Voltage-gated sodium channels are important sites for the neurotoxic actions of pyrethroid insecticides in mammals. The pore-forming alpha 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 alpha subunits and two auxiliary (beta) 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 alpha subunits in combination with their conspecific beta1 and beta2 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 microM 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 microM tefluthrin was fourfold 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.
Bezanilla,
Inactivation of the sodium channel. I. Sodium current experiments.
1977, Pubmed
Bezanilla,
Inactivation of the sodium channel. I. Sodium current experiments.
1977,
Pubmed
Catterall,
From ionic currents to molecular mechanisms: the structure and function of voltage-gated sodium channels.
2000,
Pubmed
Cestèle,
Molecular mechanisms of neurotoxin action on voltage-gated sodium channels.
2000,
Pubmed
Chen,
Cloning, distribution and functional analysis of the type III sodium channel from human brain.
2000,
Pubmed
Choi,
Structure-activity relationships for the action of 11 pyrethroid insecticides on rat Na v 1.8 sodium channels expressed in Xenopus oocytes.
2006,
Pubmed
,
Xenbase
Cummins,
Nav1.3 sodium channels: rapid repriming and slow closed-state inactivation display quantitative differences after expression in a mammalian cell line and in spinal sensory neurons.
2001,
Pubmed
,
Xenbase
Dong,
Insect sodium channels and insecticide resistance.
2007,
Pubmed
,
Xenbase
Felts,
Sodium channel alpha-subunit mRNAs I, II, III, NaG, Na6 and hNE (PN1): different expression patterns in developing rat nervous system.
1997,
Pubmed
Goldin,
Maintenance of Xenopus laevis and oocyte injection.
1992,
Pubmed
,
Xenbase
Goldin,
Mechanisms of sodium channel inactivation.
2003,
Pubmed
Goldin,
Resurgence of sodium channel research.
2001,
Pubmed
Goldin,
Nomenclature of voltage-gated sodium channels.
2000,
Pubmed
Harrill,
Time and concentration dependent accumulation of [3H]-deltamethrin in Xenopus laevis oocytes.
2005,
Pubmed
,
Xenbase
Joho,
Toxin and kinetic profile of rat brain type III sodium channels expressed in Xenopus oocytes.
1990,
Pubmed
,
Xenbase
Meacham,
Developmentally-regulated sodium channel subunits are differentially sensitive to alpha-cyano containing pyrethroids.
2008,
Pubmed
,
Xenbase
Meadows,
Sodium channels as macromolecular complexes: implications for inherited arrhythmia syndromes.
2005,
Pubmed
Narahashi,
Neuronal ion channels as the target sites of insecticides.
1996,
Pubmed
Patton,
The adult rat brain beta 1 subunit modifies activation and inactivation gating of multiple sodium channel alpha subunits.
1994,
Pubmed
,
Xenbase
Shafer,
Developmental neurotoxicity of pyrethroid insecticides: critical review and future research needs.
2005,
Pubmed
Shafer,
Complete inhibition of spontaneous activity in neuronal networks in vitro by deltamethrin and permethrin.
2008,
Pubmed
Shah,
Developmental expression of the novel voltage-gated sodium channel auxiliary subunit beta3, in rat CNS.
2001,
Pubmed
,
Xenbase
Smith,
Functional analysis of the mouse Scn8a sodium channel.
1998,
Pubmed
,
Xenbase
Smith,
Action of the pyrethroid insecticide cypermethrin on rat brain IIa sodium channels expressed in xenopus oocytes.
1998,
Pubmed
,
Xenbase
Soderlun,
Point mutations in homology domain II modify the sensitivity of rat Nav1.8 sodium channels to the pyrethroid insecticide cismethrin.
2001,
Pubmed
,
Xenbase
Soderlund,
Mechanisms of pyrethroid neurotoxicity: implications for cumulative risk assessment.
2002,
Pubmed
Soderlund,
The molecular biology of knockdown resistance to pyrethroid insecticides.
2003,
Pubmed
Song,
Modulation of sodium channels of rat cerebellar Purkinje neurons by the pyrethroid tetramethrin.
1996,
Pubmed
Tabarean,
Kinetics of modulation of tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels by tetramethrin and deltamethrin.
2001,
Pubmed
Tatebayashi,
Differential mechanism of action of the pyrethroid tetramethrin on tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels.
1994,
Pubmed
Thimmapaya,
Distribution and functional characterization of human Nav1.3 splice variants.
2005,
Pubmed
,
Xenbase
Trainer,
High affinity binding of pyrethroids to the alpha subunit of brain sodium channels.
1997,
Pubmed
Ulbricht,
Sodium channel inactivation: molecular determinants and modulation.
2005,
Pubmed
Vais,
A single amino acid change makes a rat neuronal sodium channel highly sensitive to pyrethroid insecticides.
2000,
Pubmed
,
Xenbase
Vais,
Activation of Drosophila sodium channels promotes modification by deltamethrin. Reductions in affinity caused by knock-down resistance mutations.
2000,
Pubmed
,
Xenbase
Whitaker,
Comparative distribution of voltage-gated sodium channel proteins in human brain.
2001,
Pubmed
Whitaker,
Distribution of voltage-gated sodium channel alpha-subunit and beta-subunit mRNAs in human hippocampal formation, cortex, and cerebellum.
2000,
Pubmed
Wolansky,
Relative potencies for acute effects of pyrethroids on motor function in rats.
2006,
Pubmed
