Effects of Decabrominated Diphenyl Ether (PBDE 209) on Voltage-Gated Sodium Channels in Primary Cultured Rat Hippocampal Neurons

摘要

Polybrominated diphenyl ethers (PBDEs) are widely used as flame-retardant additives. But the application of PBDEs has been challenged due to their toxicity, especially neurotoxicity. In this study, we investigated the effects of decabrominated diphenyl ether (PBDE 209), the major PBDEs product, on voltage-gated sodium channels (VGSCs) in primary cultured rat hippocampal neurons. Employing the whole-cell patch-clamp technique, we found that PBDE 209 could irreversibly decrease voltage-gated sodium channel currents (I_(Na)) in a very low dose and in a concentration-dependent manner. We had systematically explored the effects of PBDE 209 on I_(Na) and found that PBDE 209 could shift the activation and inactivation of I_(Na) toward hyperpolarizing direction, slow down the recovery from inactivation of I_(Na), and decrease the fraction of activated sodium channels. These results suggested that PBDE 209 could affect VGSCs, which may lead to changes in electrical activities and contribute to neurotoxicological damages. We also showed that ascorbic acid, as an antioxidant, was able to mitigate the inhibitory effects of PBDE 209 on VGSCs, which suggested that PBDE 209 might inhibit I_(Na) through peroxidation. Our findings provide new insights into the mechanism for the neurological symptoms caused by PBDE 209.