Unmodified CdSe quantum dots induce elevation of cytoplasmic calcium levels and impairment of functional properties of sodium channels in rat primary cultured hippocampal neurons.
Unmodified CdSe quantum dots induce elevation of cytoplasmic calcium levels and impairment of functional properties of sodium channels in rat primary cultured hippocampal neurons.
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DOI：
10.1289/ehp.11225
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发表时间：
2008-07
影响因子：
10.4
通讯作者：
Ruan DY
中科院分区：
文献类型：
--
作者：
Tang M;Xing T;Zeng J;Wang H;Li C;Yin S;Yan D;Deng H;Liu J;Wang M;Chen J;Ruan DY
纳米技术产品，如量子点（QD）的日益增长的应用，增加了接触的可能性。此外，它们在生物环境中的积累和在细胞和组织中的保留引起了人们对这些纳米技术产品潜在有害副作用的日益担忧。以前关于QD细胞毒性的研究集中在QD产生的活性氧。QD引起的细胞内钙稳态失调也可能是QD细胞毒性的原因。同时，量子点对电压门控钠通道（VGSC）电流（INa）的干扰可能导致电活动的改变，加重神经毒性损伤。我们的目的是调查潜在的神经毒性的镉硒量子点在海马神经元培养模型，重点是细胞质钙水平和VGSC功能。我们使用共聚焦激光扫描和标准的全细胞膜片钳技术。我们发现，a）QD剂量依赖性地诱导神经元死亡; B）QD处理的细胞质钙水平在较长时间内升高，这是由于细胞外钙内流和内质网的内部钙释放;和c）QD处理增强了INa的激活和失活，延长了激活的时间过程，减慢了INa的恢复，并减少了可用VGSC的分数。这项研究的结果为QD毒理学提供了新的见解，并揭示了其未来在生物学和医学中应用的潜在风险。
The growing applications of nanotechnologic products, such as quantum dots (QDs), increase the likelihood of exposure. Furthermore, their accumulation in the bioenvironment and retention in cells and tissues are arousing increasing worries about the potentially harmful side effects of these nanotechnologic products. Previous studies concerning QD cytotoxicity focused on the reactive oxygen species produced by QDs. Cellular calcium homeostasis dysregulation caused by QDs may be also responsible for QD cytotoxicity. Meanwhile the interference of QDs with voltage-gated sodium channel (VGSC) current (INa) may lead to changes in electrical activity and worsen neurotoxicologic damage. We aimed to investigate the potential for neurotoxicity of cadmium selenium QDs in a hippocampal neuronal culture model, focusing on cytoplasmic calcium levels and VGSCs function. We used confocal laser scanning and standard whole-cell patch clamp techniques. We found that a) QDs induced neuron death dose dependently; b) cytoplasmic calcium levels were elevated for an extended period by QD treatment, which was due to both extracellular calcium influx and internal calcium release from endoplasmic reticulum; and c) QD treatment enhanced activation and inactivation of INa, prolonged the time course of activation, slowed INa recovery, and reduced the fraction of available VGSCs. Results in this study provide new insights into QD toxicology and reveal potential risks of their future applications in biology and medicine.
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影响因子：
10.4
作者：
Hardman R
通讯作者：
Hardman R
影响因子：
4.7
作者：
Choi, Angela O.;Brown, Shelley E.;Maysinger, Dusica
通讯作者：
Maysinger, Dusica
DOI：
10.1073/pnas.152463399
发表时间：
2002-10-01
影响因子：
11.1
作者：
Åkerman, ME;Chan, WCW;Ruoslahti, E
通讯作者：
Ruoslahti, E
影响因子：
46.9
作者：
Jaiswal, JK;Mattoussi, H;Simon, SM
通讯作者：
Simon, SM
影响因子：
16.2
作者：
Cestèle, S;Qu, YS;Catterall, WA
通讯作者：
Catterall, WA