title: Pb2+ impairs GABAergic synaptic transmission in rat hippocampal slices: a possible involvement of presynaptic calcium channels.
abstract: Pb2+ is a common pollutant that causes a wide variety of detrimental effects on developing central nervous system, including cognitive deficit. However, the mechanisms of Pb2+ neurotoxicity remain to be elucidated. GABAergic synaptic transmission in hippocampus is implicated in learning and memory. In the present study, we examined the effects of Pb2+ on GABA(A)-receptor-mediated inhibitory postsynaptic currents (IPSCs), recorded on CA1 pyramidal neurons in rat hippocampal slices, using whole-cell patch clamp recording. Pb2+ significantly inhibited the peak amplitude of evoked IPSCs and increased paired pulse ratio. In addition, Pb2+ (2-50 microM) significantly diminished the frequency of spontaneous IPSCs in a concentration-dependent manner with an IC(50) of 7.56 microM, without changing the amplitude of spontaneous IPSCs. However, Pb2+ (10 microM) did not alter the frequency and amplitude of miniature IPSCs. It was indicated that Pb2+ impaired GABAergic synaptic transmission via a presynaptic mechanism, inhibiting action potential-dependent GABA release. Interestingly, the inhibition of spontaneous IPSC frequency induced by 10 microM Pb2+ was significantly attenuated either in the presence of 100 muM Cd2+ or in a low-calcium (0.5 mM) bath. It suggested the involvement of voltage-gated calcium channels (VGCC) in Pb2+'s inhibition of GABA release. This study provided electrophysiological evidence from developing hippocampal slices to support that Pb2+ inhibited action potential-dependent GABA release by inhibiting presynaptic VGCC, which might be a mechanism for Pb2+ -induced cognitive deficit.
authors.affiliation: School of Life Sciences, University of Science and Technology of China, Hefei Anhui 230027, PR China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Xiao
authors.forename: Yan
authors.initials: Y
authors.lastname: Gu
authors.forename: Chun-Yi
authors.initials: CY
authors.lastname: Zhou
authors.forename: Lang
authors.initials: L
authors.lastname: Wang
authors.forename: Min-Min
authors.initials: MM
authors.lastname: Zhang
authors.forename: Di-Yun
authors.initials: DY
authors.lastname: Ruan
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001640:Bicuculline / Q000494:pharmacology; D002104:Cadmium / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D018756:GABA Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology*; D066298:In Vitro Techniques; D007854:Lead / Q000633:toxicity*; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques / Q000379:methods; D017729:Presynaptic Terminals / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000187:drug effects*; D013779:Tetrodotoxin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D015220:Calcium Channels; D018756:GABA Antagonists; D002104:Cadmium; D007854:Lead; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D002118:Calcium; D001640:Bicuculline