ALTERNATIVELY SPLICED ISOFORMS OF THE N-METHYL-D-ASPARTATE RECEPTOR SUBUNIT-I ARE DIFFERENTIALLY DISTRIBUTED WITHIN THE RAT SPINAL-CORD

N-Methyl-D-aspartate-activated ionotropic glutamate receptors play a c rucial role in synaptic transmission in the spinal cord. Molecular clo ning has identified two polymorphic subunits-N-methyl-D-aspartate rece ptor subunits 1 and 2-the products of alternative splicing (subunit 1a -4b) or of different genes (subunit 2 A-D). While the distribution of N-methyl-D-aspartate receptor subunit 1 splice variants is unknown in the spinal cord, that of subunit 2 appears controversial. We examined, by means of in situ hybridization, the distribution of messenger RNAs encoded by these genes in rat cervical spinal cord. Most neurons thro ughout all the laminae express predominantly type b variants of subuni t 1 (dorsal horn: 3b; ventral horn: 4b) and the 2A subunit, although s ome neurons in laminae 2 and 9 also express subunit 2B. Our findings d emonstrate that subunit 1 splice variants are differentially distribut ed in the rat cervical cord and, since they fall into two physiologica lly and pharmacologically distinct groups, may reveal the distribution of antagonist- and agonist-preferring N-methyl-D-aspartate receptor s ubclasses. They also indicate the co-distribution of receptor subunits 1 and 2, suggesting the existence of heteromeric N-methyl-D-aspartate receptor complexes. Thus, in the spinal cord, different combinations of subunit 1 isoforms as well as subunit 2 may form N-metbyl-D-asparta te receptors with different physiological and pharmacological properti es. If this structural diversity of presumptive N-methyl-D-aspartate r eceptors exists in human spinal cord, it might identify potential targ ets for drug therapy.