Pb²⁺ modulates the NMDA-receptor-channel complex

The actions of Pb²⁺ on NMDA channel currents of acutely dissociated hippocampal CA1- and CA3-neurones from adult rats activated by aspartate plus glycine (asp/gly) were examined. A fast reversible and a slow irreversible response to Pb²⁺ were found. Pb²⁺ applied simultaneously with asp/gly decreased an inward current. The threshold concentration was below 2 μM, the current was reduced > 90% at concentrations over 100 μM, The decrease of the asp/gly activated current showed no voltage dependence. Opening of NMDA channels was not necessary for Pb²⁺-action, as preincubation in 50 μM Pb²⁺-containing external solution for several seconds dramatically reduced the response to asp/gly/Pb²⁺. This effect was reversed within 2 to 5 s of wash. Presence of Pb²⁺ or asp/Pb²⁺ or glycine/Pb²⁺ in the external solution did not prevent recovery of the NMDA receptor/channel complex from desensitization. Prolonged perfusion of a cell with the asp/gly/Pb²⁺-containing external solution resulted in an irreversible decrease of the asp/gly current, whereas the amplitude of the asp/gly/Pb²⁺ response did not change over the duration of an experiment. We conclude that Pb²⁺ modulates NMDA channel activity via interaction with the NMDA/glycine receptor: as a result the channel current decreases.