The sensitivity of N-methyl-D-aspartate receptors to lead inhibition is dependent on the receptor subunit composition

Pb is a potent inhibitor of N-methyl-D-aspartate (NMDA) receptors and its action is dependent on neuronal maturation. Developmentally regulated expression of NMDA receptor sub-units may underlie the changing sensitivity to Pb . In oocytes expressing in vitro transcribed cRNAs for 1 #{128}1or 1 #{128}2NMDA receptor subunits, Pb inhibited glutamate-activated currents with IC50 values of 0.87 ± 0.25 and 1.21 ± 0.22 tiM, respec-tively, and NMDA-activated currents with IC50 values of 1.37 ± 0.47 and 1.1 1 ± 0.33 .tM, respectively. In oocytes expressing 1 #{128}1 #{128}2 subunits, the IC50 values for Pb blockade of NMDA-or glutamate-activated currents were significantly larger when compared to 1 #{128}1or 1 #{128}2combinations. Pb concentrations greater than 1 pM inhibited glutamate-activated currents with an IC50 of 6.1 ± 1.22 jiM and NMDA-activated currents with an IC50 of 6.64 ± 3.34 p.M. Pb reduced the maximal curren