Lindane but not deltamethrin blocks a component of GABA-activated chloride channels.
Effects of deltamethrin, a pyrethroid insecticide, and lindane, the gamma isomer of hexachlorocyclohexane, on the gamma-aminobutyric acid (GABA)-activated ion channels were studied using cultured neurons isolated from the newborn rat dorsal root ganglia. The neuron was voltage clamped using the whole cell patch clamp technique. Two components of inward chloride currents were generated in response to bath application of GABA. One of the components was selectively blocked by 1 x 10(-5)M lindane in a stereospecific manner, but neither component was affected by 1 x 10(-5)M deltamethrin, which drastically prolonged the voltage-activated sodium channel current. Thus, the action of lindane to stimulate the nervous system is partly because of an interaction with the GABA receptor-channel complex. The target site of deltamethrin is not the GABA receptor-channel complex but the sodium channel. The results suggest a multiplicity of the GABAA receptor-chloride channel complex.
Ogata
N
N
Department of Pharmacology, Northwestern University Medical School, Chicago, Illinois 60611.
Vogel
S M
SM
Narahashi
T
T
D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D002712:Chlorides / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects; D001556:Hexachlorocyclohexane / Q000494:pharmacology*; D007306:Insecticides / Q000494:pharmacology*; D007473:Ion Channels / Q000187:drug effects*; D008564:Membrane Potentials; D009474:Neurons / Q000187:drug effects; D009570:Nitriles; D011722:Pyrethrins / Q000494:pharmacology*; D051381:Rats; D012964:Sodium / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D002712:Chlorides; D007306:Insecticides; D007473:Ion Channels; D009570:Nitriles; D011722:Pyrethrins; C017180:decamethrin; D005680:gamma-Aminobutyric Acid; D001556:Hexachlorocyclohexane; D012964:Sodium