CHARACTERIZATION OF DESENSITIZATION IN RECOMBINANT N-METHYL-D-ASPARTATE RECEPTORS - COMPARISON WITH NATIVE RECEPTORS IN CULTURED HIPPOCAMPAL-NEURONS

In the present study we have characterized the effect of Ca2+, glycine , and agonist concentration on inactivation and desensitization in nat ive and recombinant N-methyl-D-aspartate (NMDA) receptors. In agreemen t with earlier studies on neurons, we found that in the presence of sa turating glycine concentrations, lowering [Ca2+](o), will decrease ina ctivation of NMDA receptors in cultured hippocampal neurons. However, unlike native NMDA receptors under the same recording conditions, reco mbinant receptors did not exhibit Ca2+-dependent inactivation. We also show that the glycine-insensitive desensitization observed in the rec ombinant receptors is subunit dependent, as NR1a2A and NR1a2B receptor s significantly desensitized while the NR1a2C combination hid not. Fur thermore, we show this form of desensitization in NR1a2A receptors is due to classic agonist-induced desensitization. In addition, we demons trate the presence of glycine-dependent desensitization in recombinant receptors. The ability of glycine to inhibit desensitization correlat es to the rank order of glycine's affinity for potentiating the peak r esponse for each subtype. Finally, using ifenprodil in the presence of high and low glycine concentrations, we present evidence that both 2A -like and 2B-like subtypes of receptors can independently coexist in s ingle neurons. (C) 1998 Elsevier Science B.V. All rights reserved.