Unmodified CdSe quantum dots induce elevation of cytoplasmic calcium levels and impairment of functional properties of sodium channels in rat primary cultured hippocampal neurons.
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 (I(Na)) 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 I(Na), prolonged the time course of activation, slowed I(Na) recovery, and reduced the fraction of available VGSCs.


CONCLUSIONS
Results in this study provide new insights into QD toxicology and reveal potential risks of their future applications in biology and medicine.
Tang
Mingliang
M
School of Life Science, University of Science and Technology of China, Hefei, Anhui, People's Republic of China.
Xing
Tairan
T
Zeng
Jie
J
Wang
Huili
H
Li
Chenchen
C
Yin
Shuting
S
Yan
Dan
D
Deng
Hongmin
H
Liu
Jin
J
Wang
Ming
M
Chen
Jutao
J
Ruan
Di-Yun
DY
D000818:Animals; D019187:Cadmium Compounds / Q000633:toxicity*; D002118:Calcium / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000166:cytology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D045663:Quantum Dots; D051381:Rats; D018036:Selenium Compounds / Q000633:toxicity*; D015222:Sodium Channels / Q000378:metabolism*
D019187:Cadmium Compounds; D018036:Selenium Compounds; D015222:Sodium Channels; C058667:cadmium selenide; D002118:Calcium