| Unmodified CdSe Quantum Dots Induce Elevation of Cytoplasmic Calcium Levels and Impairment of Functional Properties of Sodium Channels in Rat Primary Cultured Hippocampal Neurons Mingliang Tang,1 Tairan Xing,1 Jie Zeng,2 Huili Wang,1 Chenchen Li,1 Shuting Yin,1 Dan Yan,1 Hongmin Deng,1 Jin Liu,1 Ming Wang,1 Jutao Chen,1 and Di-Yun Ruan1 1School of Life Science, and 2Structure Research Laboratory, University of Science and Technology of China, Hefei, Anhui, People's Republic of China Abstract
Background: 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. Objective: 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. Methods: We used confocal laser scanning and standard whole-cell patch clamp techniques. Results: 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. Conclusion: Results in this study provide new insights into QD toxicology and reveal potential risks of their future applications in biology and medicine. Key words: calcium overload, cell viability, nanoparticles, QD, voltage-gated sodium channels. Environ Health Perspect 116:915–922 (2008) . doi:10.1289/ehp.11225 available via http://dx.doi.org/ [Online 31 March 2008]
Address correspondence to D.-Y. Ruan, School of Life Science, University of Science and Technology of China, Hefei, Anhui, 230027, P.R. China. Telephone: 86 551 3606374. Fax: 86 551 3601443. E-mail: ruandy@ustc.edu.cn We thank J.-G. Hou and X.-P. Wang for providing the quantum dots. This work was supported by the National Basic Research Program of China (2002CB512907) , the National Nature Science Foundation of China (30630057, 30670554, and 30670662) , Academia Sinica (KZCX3-SW-437) , China Postdoctoral Science Foundation (20060400719) , the K.C. Wong Education Foundation of Hong Kong, and Anhui High Education Natural Science Program (ZD2008010-2) . The authors declare they have no competing financial interests. Received 2 January 2008 ; accepted 31 March 2008.
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