Xiao Cheng, Gu Yan, Zhou Chun-Yi, Wang Lang, Zhang Min-Min, Ruan Di-Yun
School of Life Sciences, University of Science and Technology of China, Hefei Anhui 230027, PR China.
Brain Res. 2006 May 9;1088(1):93-100. doi: 10.1016/j.brainres.2006.03.005. Epub 2006 Apr 21.
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.
铅离子（Pb2+）是一种常见污染物，会对发育中的中枢神经系统造成多种有害影响，包括认知缺陷。然而，Pb2+神经毒性的机制仍有待阐明。海马体中的γ-氨基丁酸（GABA）能突触传递与学习和记忆有关。在本研究中，我们使用全细胞膜片钳记录技术，检测了Pb2+对大鼠海马切片CA1锥体神经元上GABA（A）受体介导的抑制性突触后电流（IPSCs）的影响。Pb2+显著抑制诱发IPSCs的峰值幅度，并增加配对脉冲比率。此外，Pb2+（2 - 50微摩尔）以浓度依赖的方式显著降低自发IPSCs的频率，半数抑制浓度（IC50）为7.56微摩尔，而不改变自发IPSCs的幅度。然而，Pb2+（10微摩尔）并未改变微小IPSCs的频率和幅度。结果表明，Pb2+通过突触前机制损害GABA能突触传递，抑制动作电位依赖性GABA释放。有趣的是，在存在100微摩尔镉离子（Cd2+）或低钙（0.5毫摩尔）浴液的情况下，10微摩尔Pb2+诱导的自发IPSC频率抑制作用显著减弱。这表明电压门控钙通道（VGCC）参与了Pb2+对GABA释放的抑制作用。本研究提供了来自发育中海马切片的电生理证据，支持Pb2+通过抑制突触前VGCC抑制动作电位依赖性GABA释放，这可能是Pb2+诱导认知缺陷的一种机制。
