Possible mechanism of perfluorooctane sulfonate and perfluorooctanoate on the release of calcium ion from calcium stores in primary cultures of rat hippocampal neurons

Abstract

Perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) are anthropogenic compounds manufactured since the 1950s and are distributed worldwide. Now, the pollutants are being challenged by entering into the brain and the toxic effect on the central nervous system due to calcium disorder, mainly through channels on cell membrane. However, little is known about the role of calcium store in PFOS- and PFOA-evoked abnormal calcium increase. In the present study, PFOA and PFOS were measured in primary cultures of rat hippocampal neurons by LC/MS/MS analysis. Flow cytometry was used to examine altered calcium patterns in neurons labeled with fluo-3/AM and to disclose the mechanism by which PFOS and PFOA induced calcium increase in cultured neurons. The results indicate that both PFOS and PFOA can accumulate in cultured neurons and elevate calcium concentrations via release of intracellular calcium stores. Furthermore, inositol 1,4,5-trisphosphate receptors (IP3Rs) and ryanodine receptors (RyRs) were found to take part in PFOS or PFOA inducing calcium release from calcium stores. IP3Rs seem to serve a predominant role in PFOS-induced calcium release. Calcium release from intracellular stores may partially account for the perturbation of calcium homeostasis caused by PFOS or PFOA.