Selective inhibition of γ-aminobutyric acid type A receptors in human IMR-32 cells by low concentrations of toluene

Abstract

Effects of the neurotoxic organic solvent toluene on human neuronal nicotinic acetylcholine (nACh) and gaminobutyric acid type A (GABAA) neurotransmitter receptors were investigated in whole-cell voltage-clamped IMR- 32 neuroblastoma cells. Ion currents evoked by near maximum effective concentrations of 1 mM acetylcholine (ACh) and 1 mM g-aminobutyric acid (GABA) are inhibited by toluene in a concentration-dependent way. Concentration/ effect curves of toluene yield IC50 values of 2769/26 and 399/6 mM and slope factors of 1.49/0.2 and 0.89/0.1 for inhibition of the ACh- and GABA-induced ion currents, respectively. The results demonstrate the selective inhibition of human GABAA receptors by toluene at concentrations comparable with brain concentrations associated with occupational exposure.