Sodium and GABA-activated channels as the targets of pyrethroids and cyclodienes

T. Narahashi, J. M. Frey, Kenneth S Ginsburg, M. L. Roy

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

The symptoms of poisoning by the pyrethroid and cyclodiene insecticides are characterized by hyperexcitation and convulsions followed by paralysis. The main target site of the pyrethroids has been identified to be the sodium channels which are kept open for unusually long periods of time, causing a prolonged sodium current to flow which, in turn, leads to hyperexcitation of the nervous system. We have now found large differential sensitivity to the pyrethroids in two types of sodium channels. The dorsal root ganglion neurons of the rat were endowed with two types of sodium channels, one sensitive to the blocking action of tetrodotoxin (TTX) and the other insensitive to TTX. The type I pyrethroid allethrin and the type II pyrethroid deltamethrin were both effective in prolonging the sodium current in the TXX-resistant sodium channel but had only a small effect on the TTX-sensitive sodium channel. These two types of sodium channels also exhibited marked differences in their physiological properties, including the time course of current, the activation voltage, and the steady-state inactivation. In contrast to the pyrethroids, lindane and the cyclodienes endrin, isobenzan, dieldrin and heptachlor-epoxide suppressed the GABA-induced chloride current. The initial transient component of the chloride current was blocked more than the late sustained component. The suppression of the GABA-mediated synaptic inhibition would cause hyperexcitation of the nervous system. The results are compatible with the convulsant action of these insecticides.

Original languageEnglish (US)
Pages (from-to)429-436
Number of pages8
JournalToxicology Letters
Volume64-65
Issue numberC
DOIs
StatePublished - 1992
Externally publishedYes

Fingerprint

Pyrethrins
Sodium Channels
gamma-Aminobutyric Acid
Sodium
Tetrodotoxin
Neurology
Insecticides
Nervous System
Chlorides
Allethrin
Heptachlor Epoxide
Endrin
Dieldrin
Convulsants
Lindane
Spinal Ganglia
Paralysis
Poisoning
Neurons
Rats

Keywords

  • Dieldrin
  • GABA receptor channel
  • Lindane
  • Pyrethroids
  • Sodium channel

ASJC Scopus subject areas

  • Toxicology

Cite this

Sodium and GABA-activated channels as the targets of pyrethroids and cyclodienes. / Narahashi, T.; Frey, J. M.; Ginsburg, Kenneth S; Roy, M. L.

In: Toxicology Letters, Vol. 64-65, No. C, 1992, p. 429-436.

Research output: Contribution to journalArticle

Narahashi, T. ; Frey, J. M. ; Ginsburg, Kenneth S ; Roy, M. L. / Sodium and GABA-activated channels as the targets of pyrethroids and cyclodienes. In: Toxicology Letters. 1992 ; Vol. 64-65, No. C. pp. 429-436.
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AB - The symptoms of poisoning by the pyrethroid and cyclodiene insecticides are characterized by hyperexcitation and convulsions followed by paralysis. The main target site of the pyrethroids has been identified to be the sodium channels which are kept open for unusually long periods of time, causing a prolonged sodium current to flow which, in turn, leads to hyperexcitation of the nervous system. We have now found large differential sensitivity to the pyrethroids in two types of sodium channels. The dorsal root ganglion neurons of the rat were endowed with two types of sodium channels, one sensitive to the blocking action of tetrodotoxin (TTX) and the other insensitive to TTX. The type I pyrethroid allethrin and the type II pyrethroid deltamethrin were both effective in prolonging the sodium current in the TXX-resistant sodium channel but had only a small effect on the TTX-sensitive sodium channel. These two types of sodium channels also exhibited marked differences in their physiological properties, including the time course of current, the activation voltage, and the steady-state inactivation. In contrast to the pyrethroids, lindane and the cyclodienes endrin, isobenzan, dieldrin and heptachlor-epoxide suppressed the GABA-induced chloride current. The initial transient component of the chloride current was blocked more than the late sustained component. The suppression of the GABA-mediated synaptic inhibition would cause hyperexcitation of the nervous system. The results are compatible with the convulsant action of these insecticides.

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