Vol. 299, Issue 1, 171-177, October 2001

Nanomolar Concentrations of Tri-n-butyltin Facilitate -Aminobutyric Acidergic Synaptic Transmission in Rat Hypothalamic Neurons

Kiyonori Kishimoto, Shin-Ichiro Matsuo, Yumiko Kanemoto, Hitoshi Ishibashi, Yasuo Oyama and Norio Akaike

Department of Cellular and System Physiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan (K.K., S.M., Y.K., H.I., N.A.); and Laboratory of Cellular Signaling, Faculty of Integrated Arts and Sciences, University of Tokushima, Tokushima, Japan (Y.O.)

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 -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 µM 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.