Glycine and calcium-dependent effects of lead on N-methyl-D-aspartate receptor function in rat hippocampal neurons. J Pharmacol Exp Ther 279(1):143–153

The effects of lead (Pb) on N-methyl-D-aspartate (NMDA) receptor function of rat hippocampal neurons in culture were studied by use of the whole-cell patch-clamp technique. Cur-rents activated by NMDA (1 00 M) in the presence of nonsat-urating concentrations of glycine (0.01-0.05 M) were poten-tiated in a voltage-independent manner by Pb (1-10 p.M), and the potentiation was antagonized by 50 M kynurenic acid. Increasing extracellular Ca from 1 to 1 0 mM similarly poten-tiated the NMDA-activated currents in the presence of a non-saturating concentration of glycine (0.2 SM). The potentiation of NMDA-activated currents by low micromolar concentrations of Pb may be mediated by this cation’s ability to increase the affinity of the NMDA receptor for glycine. In the presence of 10 M glycine and 2 mM Ca , Pb reduced the peak ampli