Lead inhibition of NMDA channels in native and recombinant receptors

NMDA channels are key targets for lead (Pb2+) neurotoxicity and Pb2+-induced inhibition of NMDA current is age- and subunit-dependent. In rat cerebellar granule cells maintained in high KCl, glycine affinity as well as sensitivity to ifenprodil change significantly with the days in vitro, indicating a reduction of NR2B subunit expression. Pb2+ blocked NMDA current with IC50 similar to4 muM and this effect decreased significantly during the second week in vitro. In Xenopus laevis oocytes expressing recombinant NRI-NR2A, NRI-NR2B or NRI-NR2C receptors, Pb2+ inhibited glutamate-activated currents with IC50 of 3.3, 2,5 and 4.7 muM respectively. These data indicate that Pb2+ action is dependent on subunit composition and suggest that down-regulation of the NR2B subunit is correlated to a diminished sensitivity to Pb2+ inhibition. NeuroReport 12:3121-3125 (C) 2001 Lippincott Williams & Wilkins.