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

Previous studies have demonstrated that chronic lead exposure may impair ne uronal process underlying synaptic plasticity via a direct interaction with N-methyl-D-aspartate (NMDA) receptors. The present study was carried out t o investigate the effects of lead exposure on non-NMDA (alpha -amino-3-hydr oxy-5-methyl-4-isoxazole propionic acid, AMPA/ kainate) receptors of rat hi ppocampus. Ca2+-permeable AMPA/kainate receptors in organotypic slice cultu res were evaluated by using cobalt uptake, a histochemical method that iden tifies cells expressing Ca2+-permeable non-NMDA receptors. Ten mM L-glutama te-induced cobalt accumulation was enriched in area CA1, area CA3 and in de ntate gyrus, which was totally blocked by 100 muM DL-2-amino-5-phosphonoval eric acid (AP5) and 100 muM 6-cyano-7-nitroquinoxaline-2, 3-dione (CNQX). T hree hundred muM NMDA-induced cobalt accumulation was in area CA1, area den tate gyrus and was blocked by AP5 or CNQX. One hundred muM AMPA had effects in area CA1, area CA3 and in dentate gyrus, which were blocked by CNQX, no t 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 d entate gyrus and kainate receptors enriched in area CAI, area dentate gyrus are impaired by lead exposure.