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 microM) 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 microM), and accelerated the desensitization rate of I(GABA). BPA also greatly inhibited the steady state I(GABA) induced by higher concentrations of GABA (>30 microM) 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.
Choi
In-Sun
IS
Department of Pharmacology, School of Dentistry, Kyungpook National University, Daegu 700-412, South Korea.
Cho
Jin-Hwa
JH
Park
Eun-Joo
EJ
Park
Jin-Woo
JW
Kim
Sang-Hyun
SH
Lee
Maan-Gee
MG
Choi
Byung-Ju
BJ
Jang
Il-Sung
IS
D000818:Animals; D000831:Animals, Newborn; D001559:Benzhydryl Compounds; D001640:Bicuculline / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004558:Electric Stimulation; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D018756:GABA Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D018408:Patch-Clamp Techniques; D010636:Phenols / Q000494:pharmacology*; D017966:Pyramidal Cells / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D001640:Bicuculline; D004968:Estrogens, Non-Steroidal; D018756:GABA Antagonists; D010636:Phenols; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; C006780:bisphenol A; D000098826:Bisphenol A Compounds