title: Nanomolar concentrations of tri-n-butyltin facilitate gamma-aminobutyric acidergic synaptic transmission in rat hypothalamic neurons.
abstract: Tri-n-butyltin (TBT), an environmental pollutant, is accumulated in edible mollusks and fishes. It has also become a health concern in today's society. In the present study, to elucidate the possible neurotoxic action of TBT, the effect on spontaneous gamma-aminobutyric acid (GABA) release from GABAergic nerve terminals projecting to rat ventromedial hypothalamic neurons was examined using "synaptic bouton" preparation with a nystatin perforated patch recording mode under voltage-clamp conditions. The threshold concentration of TBT to affect the synaptic transmission was 10 to 30 nM. TBT at 30 nM or higher concentrations increased the frequency of GABAergic miniature inhibitory postsynaptic currents in a dose-dependent manner, whereas the current amplitude and current kinetics were not affected. The removal of either external Ca2+ or application of Cd2+ attenuated the TBT-induced facilitation of neurotransmission. TBT at 1 microM induced an inward current in more than one-half of the cells. This current persisted even after TBT was washed out. The present results indicate that TBT at environmentally relevant concentrations (30-100 nM) facilitates the GABAergic neurotransmission in the mammalian brain and the external Ca2+ is needed in this facilitation. Because the concentration of TBT accumulated in some mollusks and fishes has been reported to reach levels of 100 nM or more, such accumulation of TBT in some mollusks and fishes is thus suggested to be hazardous to the health of humans.
authors.affiliation: Department of Cellular and System Physiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kishimoto
authors.forename: S I
authors.initials: SI
authors.lastname: Matsuo
authors.forename: Y
authors.initials: Y
authors.lastname: Kanemoto
authors.forename: H
authors.initials: H
authors.lastname: Ishibashi
authors.forename: Y
authors.initials: Y
authors.lastname: Oyama
authors.forename: N
authors.initials: N
authors.lastname: Akaike
mesh_terms: D000818:Animals; D002118:Calcium / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D007031:Hypothalamus / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009411:Nerve Endings / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000187:drug effects; D051381:Rats; D009435:Synaptic Transmission / Q000187:drug effects*; D014220:Trialkyltin Compounds / Q000494:pharmacology*; D014697:Ventromedial Hypothalamic Nucleus / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D014220:Trialkyltin Compounds; C011559:tributyltin; D005680:gamma-Aminobutyric Acid; D002118:Calcium