title: Interaction of tetramethrin and deltamethrin at the single sodium channel in rat hippocampal neurons.
abstract: Type I and type II pyrethroids are known to modulate the sodium channel to cause persistent openings during depolarization and upon repolarization. Although there are some similarities between the two types of pyrethroids in their actions on sodium channels, the pattern of modification of sodium currents is different between the two types of pyrethroids. In the present study, interactions of the type I pyrethroid tetramethrin and the type II pyrethroid deltamethrin at rat hippocampal neuron sodium channels were investigated using the inside-out single-channel patch clamp technique. Deltamethrin-modified sodium channels opened much longer than tetramethrin-modified sodium channels. When 10 microM tetramethrin was applied to membrane patches that had been exposed to 10 microM deltamethrin, deltamethrin-modified prolonged single sodium currents disappeared and were replaced by shorter openings which were characteristic of tetramethrin-modified channel openings. These single-channel data are compatible with previous whole-cell competition study between type I and type II pyrethroids. These results are interpreted as being due to the displacement of the type II pyrethroid molecule by the type I pyrethroid molecule from the same binding site or to the allosteric interaction of the two pyrethroid molecules at separate sodium channel sites.
authors.affiliation: Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, Chicago, IL 60611-3008, USA.
authors.forename: H
authors.initials: H
authors.lastname: Motomura
authors.forename: T
authors.initials: T
authors.lastname: Narahashi
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004347:Drug Interactions; D004622:Embryo, Mammalian; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D007306:Insecticides / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009570:Nitriles; D011247:Pregnancy; D011722:Pyrethrins / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000378:metabolism*
chemical_list: D007306:Insecticides; D009570:Nitriles; D011722:Pyrethrins; D015222:Sodium Channels; C017180:decamethrin; C009424:tetramethrin