Impairment of the Ca2+-permeable AMPA/kainate receptors by lead exposure in organotypic rat hippocampal slice cultures.

Abstract

Previous studies have demonstrated that chronic lead exposure may impair neuronal process underlying synaptic plasticity via a direct interaction with N-methyl-D-aspartate (NMDA) receptors. The present study was carried out to investigate the effects of lead exposure on non-NMDA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid, AMPA/kainate) receptors of rat hippocampus. Ca2+-permeable AMPA/kainate receptors in organotypic slice cultures were evaluated by using cobalt uptake, a histochemical method that identifies cells expressing Ca2+-permeable non-NMDA receptors. Ten mM L-glutamate-induced cobalt accumulation was enriched in area CA1, area CA3 and in dentate gyrus, which was totally blocked by 100 microM DL-2-amino-5-phosphonovaleric acid (AP5) and 100 microM 6-cyano-7-nitroquinoxaline-2, 3-dione (CNQX). Three hundred microM NMDA-induced cobalt accumulation was in area CA1, area dentate gyrus and was blocked by AP5 or CNQX. One hundred microM AMPA had effects in area CA1, area CA3 and in dentate gyrus, which were blocked by CNQX, not by AP5. Furthermore, cobalt accumulations induced by NMDA and AMPA in the lead-exposed rats decreased significantly than those in the controls. The results indicate that AMPA receptors enriched in area CA1, area CA3, area dentate gyrus and kainate receptors enriched in area CA1, area dentate gyrus are impaired by lead exposure.