Hydroxylated PCB induces Ca2+ oscillations and alterations of membrane potential in cultured cortical cells
Hydroxylated PCB induces Ca2+ oscillations and alterations of membrane potential in cultured cortical cells
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DOI：
10.1002/jat.1501
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发表时间：
2010-05-01
影响因子：
3.3
通讯作者：
Koibuchi, Noriyuki
中科院分区：
文献类型：
--
作者：
Londono, Marina;Shimokawa, Noriaki;Koibuchi, Noriyuki
多氯联苯（PCBs）被认为是可能对健康造成不利影响的环境污染物。虽然一些同系物已被证明会影响大脑发育或功能，但介导其毒性的分子机制尚未完全了解。由于细胞内Ca2+的信号转导对神经元的发育和可塑性至关重要，我们研究了多氯联苯对培养的小鼠皮质细胞Ca2+稳态和膜电位的影响。急性暴露于羟基化PCB 106 [4(OH)-2',3,3',4',5'-五氯联苯，OH-PCB 106, 0.1 μ M]引起反复出现的Ca2+振荡，分为三种原型。尽管细胞外Ca2+剥夺显著降低了振荡，但54%的细胞仍表现出不同的振荡模式或细胞内Ca2+浓度逐渐增加，表明可能以细胞特异性的方式参与多个Ca2+通道。对几种通道/受体阻滞剂（包括硝苯地平、良诺定、xestospongine和河豚毒素）的不同反应进一步证实了这种可能性。虽然所有化学物质在不同的神经元亚群中都有部分抑制作用，但硝苯地平在最大的细胞亚群中阻断了OH-PCB 106的作用，其程度最大。Ryanodine也以相似的程度阻断了这一作用，但作用于较小的细胞亚群。此外，OH-PCB 106在所有记录的细胞中诱导质膜去极化。综上所述，我们的研究结果表明OH-PCB 106通过诱导细胞外内流和/或细胞内释放Ca2+来改变膜电位和Ca2+动力学。这些机制可能与它们的神经毒性有关。版权所有John Wiley & Sons， Ltd. 2009
Polychlorinated biphenyls (PCBs) are known as environmental pollutants that may cause adverse health effects. Although some congeners have been shown to affect brain development or function, the molecular mechanisms mediating their toxicity are not yet fully understood. Since signal transduction via intracellular Ca2+ is crucial for neuronal development and plasticity, we investigated the effect of PCBs on Ca2+ homeostasis and membrane potential in cultured mouse cortical cells. Acute exposure to hydroxylated PCB 106 [4(OH)-2',3,3',4',5'-pentachlorobiphenyl, OH-PCB 106, 0.1 mu M] caused recurring Ca2+ oscillations that were classified into three prototypes. Although extracellular Ca2+ deprivation significantly reduced the oscillations, 54% of the cells still showed different patterns of oscillations or gradual increase in the intracellular Ca2+ concentration, indicating possible involvement of multiple Ca2+ channels in a cell-specific manner. Such a possibility was further confirmed by differential responses to several channel/receptor blockers, including nifedipine, ryanodine, xestospongine and tetrodotoxin. Although all chemicals had partial inhibition action in different subsets of neurons, nifedipine blocked the OH-PCB 106 action in the largest subpopulation of cells and with the greatest magnitude. Ryanodine also blocked the action with a similar magnitude, but in a smaller subpopulation of cells. Moreover, OH-PCB 106 induced depolarization of the plasma membrane in all the recorded cells. Taken together, our results indicate that OH-PCB 106 alters membrane potential as well as Ca2+ dynamics in part by inducing extracellular influx and/or intracellular release of Ca2+. These mechanisms may be responsible for their neurotoxicity. Copyright (C) 2009 John Wiley & Sons, Ltd.