Mechanisms of unmodified CdSe quantum dot-induced elevation of cytoplasmic calcium levels in primary cultures of rat hippocampal neurons

Quantum dots (QDs) have shown great promise for applications in biology and medicine, which is being challenged by their potential nanotoxicity. Reactive oxygen species (ROS) produced by QDs are believed to be partially responsible for QD cytotoxicity. Cytoplasmic Ca2+ plays an important role in the development of ROS injury. Here we found unmodified cadmium selenium (CdSe) QDs could elevate cytoplasmic calcium levels ([Ca2+]i) in primary cultures of hippocampal neurons, involved both extracellular Ca2+ influx and internal Ca2+ release. More specifically, verapamil and mibefradil (L-type and T-type calcium channels antagonists, respectively) failed to prevent extracellular Ca2+ influx under QD insult, while ω-conotoxin (N-type antagonist) could partially block this Ca2+ influx. Surprisingly, this Ca2+ influx could be well blocked by voltage-gated sodium channels (VGSCs) antagonist, tetrodotoxin (TTX). QD-induced internal Ca2+ release could be avoided by clonazepam, a specific inhibitor of mitochondrial sodium–calcium exchangers (MNCX), and also by TTX. Furthermore, dantrolene, an antagonist of ryanodine (Ry) receptors in endoplasmic reticulum (ER), almost abolished internal Ca2+ release, while 2-APB [inositol triphosphate (IP3) receptors antagonist] failed to block this Ca2+ release, indicating that released Ca2+ from mitochondria, which was induced by extracellular Na+ influx, further triggered much more Ca2+ release from ER. Our results imply that more research on the biocompatibility and biosafety of QD is both warranted and necessary.