Objective To examine the effects of Pd^2+ on N-methyl-D-aspartate(NMDA)-,K^+-and quisqualate(QA)/kainite(KA)-induced increases in intracellular free calcium concentration([Ca^2+]I)in cultured fetal rat hippocampal neureons in order to explain the cognitive and learning deficits produced by this heavy metal.Methods Laser scanning confocal microscopy was used.Results The results clearly demonstrated that adding Pd^2+ before or after NMDA/glycine stimulation selectively inhibited the stimulated increases in [Ca^2+]I in a concemntration-dependent manner.In contrast,Pb^2+ treatment did not markedly affect increases in [Ca^2+]I indced by an admixture of QA and KA.The minimal inhibitory effect of Pb^2+ occurred at 1 μmol/L,and more than seventy percent abolition of the NMDA-stimulated increase in [Ca^2+]I was observed at 100μmol/L Pb^2+.Evaluation of Pb^2+ induced increase in [Ca^2+]I response to elevating extracellular concentration of NMDA,glycine or calcium revealed that Pb^2+ was a noncompetitive antagonist of both NMDA and glycine,and a competitive antagonist of Ca^2+ at NMDA receptor chamels.In addition,Pb^2+ inhibited depolarization-evoked increases in [Ca^2+]I mediated by K^+ stimulation (30μmol/L),indicating that Pb^2+ also depressed the voltage-dependent calcium channels.Also ,the results showed that Pb^2+ appeared to be able to elevate the resting levels of [Ca^2+]I in cultured neurons,implying a reason for Pb^2+-enhanced spontaneous release of several neurotransmitters reported in intracellular[Ca^2+]I cultured hippocampal neurons.
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