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长期接触铅会导致细胞培养中的神经元电膜特性发生持续性改变。

Chronic exposure to lead causes persistent alterations in the electric membrane properties of neurons in cell culture.

作者信息

Scott B, Lew J

出版信息

J Neurobiol. 1985 Nov;16(6):425-33. doi: 10.1002/neu.480160603.

Abstract

The effects of chronic lead (Pb) exposure on neuronal electric membrane properties (EMP) were determined using neural cell cultures of adult mouse dorsal root ganglia (DRG). Cultures were exposed to Pb concentrations ranging from 0 to 100 microM for 12 days (8 DIV to 20 DIV). EMP were determined in Pb-free medium either immediately after withdrawal (IWD), or 6 days after withdrawal (6WD) from Pb. For IWD, regression analysis indicated that a number of EMP varied significantly with increasing Pb concentration. The largest such change occurred for electrical excitability which decreased significantly with increasing Pb (P = 0.000), being reduced by approximately two-thirds for neurons exposed to 100 microM Pb; resting membrane potential increased with Pb (P = 0.000); membrane time constant decreased with Pb (P = 0.007); action potential afterhyperpolarization decreased with Pb (P = 0.023). There was also evidence that the time course of action potentials was accelerated with increasing Pb concentrations, the rate of fall of neurons with biphasic falling phases being particularly increased (P = 0.047). This general pattern of altered EMP was observed for the 6WD condition also, indicating that chronic exposure to Pb caused persistent abnormalities in neuronal membranes even after 6 days of cultivation in Pb-free medium. The patterns of alterations in EMP suggested that chronic Pb exposure caused a prolonged increase in potassium permeability. It was proposed that the latter was mediated through a Pb-induced increase in intracellular ionic calcium and the associated disruption of calcium homeostasis.

摘要

利用成年小鼠背根神经节(DRG)的神经细胞培养物,确定了慢性铅(Pb)暴露对神经元电膜特性(EMP)的影响。将培养物暴露于浓度范围为0至100微摩尔的铅中12天(从第8天体外培养至第20天体外培养)。在无铅培养基中,于撤铅后立即(撤铅后立即,IWD)或撤铅6天后(撤铅6天后,6WD)测定EMP。对于撤铅后立即测定,回归分析表明,一些EMP随铅浓度增加而有显著变化。其中最大的变化发生在电兴奋性方面,电兴奋性随铅浓度增加而显著降低(P = 0.000),对于暴露于100微摩尔铅的神经元,电兴奋性降低了约三分之二;静息膜电位随铅浓度增加而升高(P = 0.000);膜时间常数随铅浓度增加而降低(P = 0.007);动作电位超极化后电位随铅浓度增加而降低(P = 0.023)。也有证据表明,动作电位的时间进程随着铅浓度增加而加快,具有双相下降阶段的神经元的下降速率尤其增加(P = 0.047)。在撤铅6天后的情况下也观察到了这种EMP改变的总体模式,这表明即使在无铅培养基中培养6天后,慢性铅暴露仍会导致神经元膜持续出现异常。EMP的改变模式表明,慢性铅暴露导致钾通透性长期增加。有人提出,后者是通过铅诱导的细胞内离子钙增加以及相关的钙稳态破坏介导的。

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