Sodium channels and GABAA receptor-channel complex as targets of environmental toxicants

Toxicology Letters
T NarahashiH Tatebayashi

Abstract

Voltage-activated sodium channels and GABAA receptor-chloride channel complex are among the most important target sites of various environmental neurotoxicants. Pyrethroids keep the sodium channels open for prolonged periods of time leading to hyperexcitation of the entire nervous system. In rat cerebellar Purkinje neurons and dorsal root ganglion neurons, only about 1% of sodium channel population needed to be modified by the pyrethroid tetramethrin to increase the depolarizing after-potential to the level of the threshold membrane potential for generation of repetitive after-discharges. This concept of toxicity amplification is applicable to other chemicals that go through a threshold phenomenon to exert their effects. The potency of pyrethroids on neuronal sodium channels increased with lowering the temperature with a Q10 value of 0.2. The selective pyrethroid toxicity between mammals and insects can be quantitatively explained on the basis of the differences in 5 factors, i.e. the intrinsic sodium channel sensitivity, the sodium channel modification due to temperature difference, the reversibility of sodium channel, the detoxication of pyrethroids, and body size. These 5 factors are multiplied to approximately 2000 which is...Continue Reading

References

Jun 1, 1992·Trends in Pharmacological Sciences·T Narahashi
Apr 14, 1984·The Veterinary Record·R Titchener
Jan 1, 1994·Annual Review of Neuroscience·R L Macdonald, R W Olsen

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Citations

Dec 1, 1995·Toxicology Letters·E K Silbergeld
Sep 24, 1999·Neurotoxicology and Teratology·A C MonizM M Bernardi
Dec 16, 2004·The Journal of Reproduction and Development·Soon-Sun KimKui-Lea Park
Mar 10, 2010·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP·Ryo KamataHiroaki Shiraishi
Jul 14, 2016·Environmental Science and Pollution Research International·Fernanda Craveiro FrancoDaniela de Melo E Silva
Jan 22, 2008·Neurotoxicology and Teratology·M J Wolansky, J A Harrill
Feb 27, 2007·Neurotoxicology and Teratology·M J WolanskyK M Crofton
Jan 16, 2007·Toxicon : Official Journal of the International Society on Toxinology·Graham M Nicholson
Oct 9, 2009·Toxicological Sciences : an Official Journal of the Society of Toxicology·Victor BrizCristina Suñol
Sep 27, 2005·Toxicological Reviews·Sally M BradberryJ Allister Vale
Jul 1, 2006·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Jason R RichardsonGary W Miller
Mar 25, 2018·Environmental Science and Pollution Research International·Doha Yahia, Marwa F Ali

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