PREFERENTIAL COASSEMBLY OF RECOMBINANT NMDA RECEPTORS COMPOSED OF 3 DIFFERENT SUBUNITS

cDNAS ENCODING NMDA receptor subunits have recently been cloned and be en shown to have different distributions in the CNS. However, no studi es on the possible in vivo combinations or subunit stoichiometry have yet been carried out. By combining human NR1 with rat NR2A and NR2C we have studied the pharmacological properties of three possible NMDA re ceptor subtypes; NR1 + NR2A, NR1 + NR2C and NR1 + NR2A + NR2C. By perf orming glycine concentration-response curves and comparing EC50s, it w as possible to show that the NR1 + NR2A + NR2C receptor preferentially co-assembled when all three subunit cDNAs were present. This receptor had an affinity for glycine intermediate between that of NR1 + NR2A a nd NR1 + NR2C, but a similar Hill coefficient. Thus, two different NR2 subunits can combine in the same receptor, conferring unique pharmaco logical properties, suggesting that it is likely that two or more NR2 subunits co-assemble together in the same NMDA receptor complex.