GABA_A Receptor Subunit Composition Drives Its Sensitivity to the Insecticide Fipronil.

ABSTRACT: Fipronil (FPN) is a worldwide-used neurotoxic insecticide, targeting, and blocking GABA_A receptors (GABA_ARs). Beyond its efficiency on insect GABA_ARs, FPN causes neurotoxic effects in humans and mammals. Here, we investigated the mode of action of FPN on mammalian α6-containing GABA_ARs to understand its inhibitory effects on GABA-induced currents, as a function of the synaptic or extrasynaptic localization of GABA_ARs. We characterized the effects of FPN by electrophysiology using Xenopus oocytes which were microtransplanted with cerebellum membranes or injected with α6β3, α6β3γ2S (synaptic), and α6β3δ (extrasynaptic) cDNAs. At micromolar concentrations, FPN dose-dependently inhibited cerebellar GABA currents. FPN acts as a non-c

SUBMITTER: Soualah Z 

PROVIDER: S-EPMC8668240 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature