The effect of CdSe–ZnS quantum dots on calcium currents and catecholamine secretion in mouse chromaffin cells

Abstract

a b s t r a c tSemiconductor nanocrystal quantum dots (QDs) possess an enormous potential of applications in nanomedicine, drug delivery and bioimaging which derives from their unique photoemission and photostability characteristics. In spite of this, however, their interactions with biological systems and impact on human health are still largely unknown. Here we used neurosecretory mouse chromaffin cells of the adrenal gland for testing the effects of CdSeeZnS coreeshell quantum dots (5e36 nM) on Ca 2þ channels functionality and Ca 2þ -dependent neurosecretion. Prolonged exposure (24 h) to commonly used concentrations of CdSeeZnS QDs (!16 nM) showed that the semiconductor nanocrystal is effectively internalized into the cells without affecting cell integrity (no changes of membrane resistance and cell capacitance). QDs reduced the size of Ca 2þ currents by w28% in a voltage-independent manner without affecting channel gating. Correspondingly, depolarization-evoked exocytosis, measured at þ10 mV, where Ca 2þ currents are maximal, was reduced by 29%. CdSeeZnS QDs reduced the size of the readily releasable pool (RRP) of secretory vesicles by 32%, the frequency of release by 33% and the overall quantity of released catecholamines by 61%, as measured by carbon fibers amperometry. In addition, the Ca 2þ -dependence of exocytosis was reduced, whereas the catecholamine content of single granules, as well as the kinetics of release, remained unaltered. These data suggest that exposure to CdSeeZnS QDs impairs Ca 2þ influx and severely interferes with the functionality of the exocytotic machinery, compromising the overall catecholamine supply from chromaffin cells.

The Effects of Nanomaterials as Endocrine Disruptors

“…This is fundamental for an assessment of the endocrine toxicity of NPs, but unfortunately much of this characterization is largely lacking in current studies. For example, most available studies provide an indication of the chemical composition and size of the NPs used, while only a few of the reviewed studies go beyond this basic information to include data on other parameters such as functionalization [37,39,42–44,57,69,78,81,82,84,94,120,121,123], number concentration [33,34,49,58,60,89,96], surface area [35,36,70,79,86,88], shape [72] and degree of aggregation [85]. …”

“…In fact, the results of this study showed that noble metal NPs disrupt exocytosis, typically by altering the number of molecules and release kinetics, and enhance direct disruption of the vesicle matrix [123]. The functionality of the exocytotic machinery of mouse (C57BL/6J) chromaffin cells was also severely damaged by exposure to 5–36 nM of carboxyl QDs with CdSe core and ZnS shell since these were able to impair Ca 2+ influx and consequently compromise the overall catecholamine supply from chromaffin cells [120]. Interestingly, Ag-NP (coated with citrate or polyvinylpyrrolidone) exposure (30 μM) also impairs neurodevelopment in PC12 cells as demonstrated by a depleted emergence of the acetylcholine-phenotype and an enhanced differentiation into a DA-phenotype after treatment with citrate-coated Ag-NPs and polyvinylpyrrolidone-coated Ag-NPs, respectively [121].…”

Interaction of SiO2 nanoparticles with neuronal cells: Ionic mechanisms involved in the perturbation of calcium homeostasis

“…It has been reported that some NPs, such as uncoated CdSe quantum dots (QDs), can irreversibly disrupt calcium homeostasis in neuronal cells by affecting voltage dependent Na + and N-type Ca 2+ channels (Tang et al, 2008a(Tang et al, , 2008b; conversely, CdSe-ZnS QDs can reduce calcium influx through Ca 2+ VDCCs (Gosso et al, 2011). GT1-7 cells express variable extents of many types of VDCCs (Charles and Hales, 1995;Hoddah et al, 2009;Watanabe et al, 2004).…”

Quantum Dot Cytotoxicity and Ways To Reduce It

“…21 More recently, CdSe/ZnS QDs were shown to increase intracellular Ca 2þ in rat hippocampal neurons 22 and in mouse chromaffin cells. 23 Studies of renal epithelial cells exposed to QDs have revealed that F-actin binds to QDs and can be depolymerized by Cd 2þ ions. 24 Since F-actin is postulated to play a role in controlling secretory granule access to the plasma membrane, it is possible that the reduced neurosecretion may be due to F-actin impairment by QDs and/or released Cd 2þ .…”