Alternatively spliced isoforms of the N-methyl-D-aspartate receptor subunit 1 are differentially distributed within...

N-Methyl-D-aspartate-activated ionotropic glutamate receptors play a crucial role in synaptic transmission in the spinal cord. Molecular cloning has identified two polymorphic subunits--N-methyl-D-aspartate receptor 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 throughout all the laminae express predominantly type b variants of subunit 1 (dorsal horn: 3b; ventral horn: 4b) and the 2A subunit, although some neurons in laminae 2 and 9 also express subunit 2B. Our findings demonstrate that subunit 1 splice variants are differentially distributed in the rat cervical cord and, since they fall into two physiologically and pharmacologically distinct groups, may reveal the distribution of antagonist- and agonist-preferring N-methyl-D-aspartate receptor subclasses. 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-methyl-D-aspartate receptors with different physiological and pharmacological properties. If this structural diversity of presumptive N-methyl-D-aspartate receptors exists in human spinal cord, it might identify potential targets for drug therapy.