Multiple effects of bisphenol A, an endocrine disrupter, on GABAA receptors in acutely dissociated rat CA3 pyramidal neurons

Bisphenol A (BPA), an endocrine disrupter, is contained in cans, polycarbonate bottles and some dental sealants. While the toxicological effects of BPA on the endocrine system have been extensively studied, its action on the central nervous system is poorly understood. Herein, we report the effects of BPA on GABA-induced currents (IGABA), using a conventional whole-cell patch clamp technique from acutely isolated rat CA3 pyramidal neurons. By itself, BPA concentration-dependently elicited the membrane current, which was significantly blocked by bicuculline, a selective GABAA receptor antagonist. BPA potentiated the peak IGABA induced by lower concentrations of GABA (<10 μM) in a concentration-dependent manner. The extent of BPA-induced potentiation of IGABA was significantly reduced by either diazepam or ethanol, allosteric modulators of GABAA receptors. BPA, however, inhibited the peak IGABA induced by higher concentrations of GABA (>30 μM), and accelerated the desensitization rate of IGABA. BPA also greatly inhibited the steady state IGABA induced by higher concentrations of GABA (>30 μM) in a noncompetitive manner. In addition, BPA affected synaptic GABAA receptors as it decreased the amplitude of GABAergic miniature inhibitory postsynaptic currents in a concentration-dependent manner. Considering its complex modulatory effects on GABAA receptors, BPA might have potential toxicological effects on the central nervous system.