DEVELOPMENTAL-CHANGES IN NMDA RECEPTOR GLYCINE AFFINITY AND IFENPRODIL SENSITIVITY REVEAL 3 DISTINCT POPULATIONS OF NMDA RECEPTORS IN INDIVIDUAL RAT CORTICAL-NEURONS

Previous work with recombinant receptors has shown that the identity o f the NMDA NR2 subunit influences receptor affinity for both glutamate and glycine. We have investigated the developmental change in NMDA re ceptor affinity for both glutamate and glycine in acutely dissociated parietal cortex neurons of the rat, together with the expression durin g ontogeny of NR2A and NR2B mRNA and protein. Whereas there is little change in NMDA receptor glutamate affinity with age, a population of N MDA receptors emerges in 14- and 28-d-old animals with a markedly redu ced affinity for glycine (mK(D) = similar to 800 nM) and a reduced sen sitivity to the NR2B subunit-selective NMDA antagonist ifenprodil. The se changes are paralleled by a developmental increase in the expressio n of NR2A. Thus, in mature animals a population of NMDA receptors appe ars with a lower affinity for glycine that might not be saturated unde r normal physiological conditions. Ifenprodil (10 mu M) inhibits virtu ally all of the NMDA receptor-evoked current in very young neurons tha t contain a single population of receptors exhibiting a high affinity for glycine (mK(D) = similar to 20 nM). In older neurons, which contai n NMDA receptors with both high and low affinities for glycine, ifenpr odil (10 mu M) inhibits both the high-affinity population and a signif icant proportion of the low-affinity component, thus revealing three p harmacologically distinct populations of NMDA receptors in single neur ons. Moreover, these observations suggest that ifenprodil might bind w ith high affinity to NMDA receptors containing both NR2A and NR2B subu nits as well as those containing only NR2B.