title: Actions of the pyrethroid insecticide bifenthrin on sodium channels expressed in rat cerebral cortical neurons.
abstract: Voltage-gated sodium channels are important sites for the neurotoxic actions of pyrethroid insecticides in mammals. Here, we studied the mode of action of bifenthrin on the native sodium channels in cerebral cortical neurons prepared from newborn rat brain, where the toxic effects are largely generated. Bifenthrin caused a pronounced late current that persisted at the end of a depolarizing pulse, a slowly-decaying tail current following repolarization and significant resting modification (25.3% modification at 10 μM). No significant bifenthrin-induced effect was observed at the peak current. Bifenthrin also caused a concentration-dependent hyperpolarizing shift in steady-state activation and inactivation as well as slowed recovery from channel inactivation. Repetitive depolarization increased the potency of bifenthrin with high frequency. There was approximately 64% inhibition of modification upon repetitive activation by 10-Hz trains of depolarizing pulses. These results suggest that bifenthrin binds to and modifies sodium channels in both the closed and open states and exhibits the behavior between type I and type II.
authors.affiliation: State Key Laboratory of Integrated Pest Management, Institute of Zoology, Chinese Academy of Sciences , Beijing , PR China.
authors.forename: Lin
authors.initials: L
authors.lastname: Yang
authors.forename: Li
authors.initials: L
authors.lastname: Li
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007306:Insecticides / Q000633:toxicity*; D015640:Ion Channel Gating / Q000187:drug effects; D007700:Kinetics; D008564:Membrane Potentials; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D011722:Pyrethrins / Q000633:toxicity*; D051381:Rats; D018570:Risk Assessment; D061566:Voltage-Gated Sodium Channels / Q000187:drug effects* / Q000378:metabolism
chemical_list: D007306:Insecticides; D011722:Pyrethrins; D061566:Voltage-Gated Sodium Channels; C099952:bifenthrin
keywords: Bifenthrin; patch clamp; pyrethroid; state-dependent modification; voltage-gated sodium channel