Alternative splicing generates functionally distinct N-methyl-D-aspartate receptors.

We have used expression cloning in Xenopus oocytes to isolate two different cDNAs encoding functional N-methyl-D-aspartate (NMDA) receptor subunits. The two receptors (NMDA-R1A and -R1B) display different pharmacologic properties as a consequence of alternative exon addition within the putative ligand-binding domain. The splicing choice is regulated such that R1B is the predominant form of receptor in the cerebellum, whereas R1A predominates in other brain regions. Expression of either of the subunits alone in oocytes results in an NMDA-evoked inward current with electrophysiologic properties closely resembling those of the NMDA receptors observed in neurons. Thus, the complex properties exhibited by the NMDA receptor in neurons can be generated by the expression of a single receptor subunit.