Multiple effects of bisphenol A, an endocrine disrupter, on GABA_A 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 (I_GABA), 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 GABA_A receptor antagonist. BPA potentiated the peak I_GABA induced by lower concentrations of GABA (<10 μM) in a concentration-dependent manner. The extent of BPA-induced potentiation of I_GABA was significantly reduced by either diazepam or ethanol, allosteric modulators of GABA_A receptors. BPA, however, inhibited the peak I_GABA induced by higher concentrations of GABA (>30 μM), and accelerated the desensitization rate of I_GABA. BPA also greatly inhibited the steady state I_GABA induced by higher concentrations of GABA (>30 μM) in a noncompetitive manner. In addition, BPA affected synaptic GABA_A receptors as it decreased the amplitude of GABAergic miniature inhibitory postsynaptic currents in a concentration-dependent manner. Considering its complex modulatory effects on GABA_A receptors, BPA might have potential toxicological effects on the central nervous system.