Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Toxicol Appl Pharmacol
2011 Dec 15;2573:377-87. doi: 10.1016/j.taap.2011.09.021.
Show Gene links
Show Anatomy links
Differential state-dependent modification of rat Na(v)1.6 sodium channels expressed in human embryonic kidney (HEK293) cells by the pyrethroid insecticides tefluthrin and deltamethrin.
He B
,
Soderlund DM
.
???displayArticle.abstract???
We expressed rat Na(v)1.6 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 Na(v)1.6 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 ~25mV for tefluthrin and ~20mV for deltamethrin. The highest attainable concentrations of these compounds also caused shifts of ~5-10mV 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 Na(v)1.6 channels by determining the effect of trains of 1 to 100 5-ms depolarizing prepulses at frequencies of 20 or 66.7Hz 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 Na(v)1.6 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 Na(v)1.6 channels in HEK293 cells differ from the effects of these compounds on Na(v)1.6 channels in Xenopus oocytes and more closely reflect the actions of pyrethroids on channels in their native neuronal environment.
Ahn,
A new Nav1.7 sodium channel mutation I234T in a child with severe pain.
2010, Pubmed
Ahn,
A new Nav1.7 sodium channel mutation I234T in a child with severe pain.
2010,
Pubmed
Attwell,
The steady state TTX-sensitive ("window") sodium current in cardiac Purkinje fibres.
1979,
Pubmed
Auld,
A rat brain Na+ channel alpha subunit with novel gating properties.
1988,
Pubmed
,
Xenbase
Bezanilla,
Inactivation of the sodium channel. I. Sodium current experiments.
1977,
Pubmed
Breckenridge,
Evidence for a separate mechanism of toxicity for the Type I and the Type II pyrethroid insecticides.
2009,
Pubmed
,
Xenbase
Burbidge,
Molecular cloning, distribution and functional analysis of the NA(V)1.6. Voltage-gated sodium channel from human brain.
2002,
Pubmed
Caldwell,
Sodium channel Na(v)1.6 is localized at nodes of ranvier, dendrites, and synapses.
2000,
Pubmed
Cao,
Additivity of pyrethroid actions on sodium influx in cerebrocortical neurons in primary culture.
2011,
Pubmed
Catterall,
International Union of Pharmacology. XLVIII. Nomenclature and structure-function relationships of voltage-gated calcium channels.
2005,
Pubmed
Chen,
Functional properties and differential neuromodulation of Na(v)1.6 channels.
2008,
Pubmed
Chinn,
Stabilization of sodium channel states by deltamethrin in mouse neuroblastoma cells.
1986,
Pubmed
Choi,
Cyclosporin A and deltamethrin block the downregulation of Nav1.8 sodium channels expressed in Xenopus oocytes.
2004,
Pubmed
,
Xenbase
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
Dib-Hajj,
Voltage-gated sodium channels: therapeutic targets for pain.
2009,
Pubmed
Du,
Identification of a cluster of residues in transmembrane segment 6 of domain III of the cockroach sodium channel essential for the action of pyrethroid insecticides.
2009,
Pubmed
Goldin,
Resurgence of sodium channel research.
2001,
Pubmed
Graham,
Characteristics of a human cell line transformed by DNA from human adenovirus type 5.
1977,
Pubmed
Harrill,
Time and concentration dependent accumulation of [3H]-deltamethrin in Xenopus laevis oocytes.
2005,
Pubmed
,
Xenbase
He,
Human embryonic kidney (HEK293) cells express endogenous voltage-gated sodium currents and Na v 1.7 sodium channels.
2010,
Pubmed
Hu,
Distinct contributions of Na(v)1.6 and Na(v)1.2 in action potential initiation and backpropagation.
2009,
Pubmed
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
Motomura,
Interaction of tetramethrin and deltamethrin at the single sodium channel in rat hippocampal neurons.
2001,
Pubmed
O'Reilly,
Modelling insecticide-binding sites in the voltage-gated sodium channel.
2006,
Pubmed
Power,
Pyrethrin and pyrethroid exposures in the United States: a longitudinal analysis of incidents reported to poison centers.
2007,
Pubmed
Ranson,
Pyrethroid resistance in African anopheline mosquitoes: what are the implications for malaria control?
2011,
Pubmed
Schaller,
Expression and distribution of voltage-gated sodium channels in the cerebellum.
2003,
Pubmed
Shah,
Developmental expression of the novel voltage-gated sodium channel auxiliary subunit beta3, in rat CNS.
2001,
Pubmed
,
Xenbase
Shaw,
Preferential transformation of human neuronal cells by human adenoviruses and the origin of HEK 293 cells.
2002,
Pubmed
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,
Molecular mechanisms of pyrethroid insecticide neurotoxicity: recent advances.
2012,
Pubmed
Soderlund,
Mechanisms of pyrethroid neurotoxicity: implications for cumulative risk assessment.
2002,
Pubmed
Soderlund,
State-Dependent Modification of Voltage-Gated Sodium Channels by Pyrethroids.
2010,
Pubmed
,
Xenbase
Song,
Modulation of sodium channels of rat cerebellar Purkinje neurons by the pyrethroid tetramethrin.
1996,
Pubmed
Tabarean,
Potent modulation of tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels by the type II pyrethroid deltamethrin.
1998,
Pubmed
Tan,
Actions of Tefluthrin on Rat Na(v)1.7 Voltage-Gated Sodium Channels Expressed in Xenopus Oocytes.
2011,
Pubmed
,
Xenbase
Tan,
Divergent actions of the pyrethroid insecticides S-bioallethrin, tefluthrin, and deltamethrin on rat Na(v)1.6 sodium channels.
2010,
Pubmed
,
Xenbase
Tan,
Human and rat Nav1.3 voltage-gated sodium channels differ in inactivation properties and sensitivity to the pyrethroid insecticide tefluthrin.
2009,
Pubmed
,
Xenbase
Tatebayashi,
Differential mechanism of action of the pyrethroid tetramethrin on tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels.
1994,
Pubmed
Thomas,
HEK293 cell line: a vehicle for the expression of recombinant proteins.
2005,
Pubmed
Usherwood,
Mutations in DIIS5 and the DIIS4-S5 linker of Drosophila melanogaster sodium channel define binding domains for pyrethroids and DDT.
2007,
Pubmed
,
Xenbase
Vais,
Activation of Drosophila sodium channels promotes modification by deltamethrin. Reductions in affinity caused by knock-down resistance mutations.
2000,
Pubmed
,
Xenbase
Vais,
A single amino acid change makes a rat neuronal sodium channel highly sensitive to pyrethroid insecticides.
2000,
Pubmed
,
Xenbase
Verschoyle,
Structure-activity relationships of some pyrethroids in rats.
1980,
Pubmed
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
Wittmack,
Fibroblast growth factor homologous factor 2B: association with Nav1.6 and selective colocalization at nodes of Ranvier of dorsal root axons.
2004,
Pubmed
Wu,
Underlying mechanism of actions of tefluthrin, a pyrethroid insecticide, on voltage-gated ion currents and on action currents in pituitary tumor (GH3) cells and GnRH-secreting (GT1-7) neurons.
2009,
Pubmed
