Pb2+ impairs GABAergic synaptic transmission in rat hippocampal slices: A possible involvement of presynaptic calcium channels
| Autor: | Di-Yun Ruan, Cheng Xiao, Lang Wang, Chun-Yi Zhou, Min-Min Zhang, Yan Gu |
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| Rok vydání: | 2006 |
| Předmět: |
Male
Patch-Clamp Techniques viruses Presynaptic Terminals Neural facilitation Tetrodotoxin In Vitro Techniques Neurotransmission Biology Hippocampal formation Bicuculline Inhibitory postsynaptic potential Hippocampus Synaptic Transmission GABA Antagonists Animals Patch clamp Rats Wistar Molecular Biology gamma-Aminobutyric Acid Neurons Dose-Response Relationship Drug Voltage-dependent calcium channel General Neuroscience virus diseases Neural Inhibition biochemical phenomena metabolism and nutrition Rats respiratory tract diseases Electrophysiology Animals Newborn Lead Biophysics GABAergic Calcium Calcium Channels Neurology (clinical) Neuroscience Cadmium Developmental Biology |
| Zdroj: | Brain Research. 1088:93-100 |
| ISSN: | 0006-8993 |
| DOI: | 10.1016/j.brainres.2006.03.005 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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