MOLECULAR DIVERSITY OF THE NMDA RECEPTOR CHANNEL

Two novel subunits of the mouse NMDA receptor channel, the epsilon-2 and epsilon-3 subunits, have been identified by cloning and expression of complementary DNAs. The heteromeric epsilon-1/zeta-1, epsilon-2/zeta-1 and epsilon-3/zeta-1 NMDA receptor channels exhibit distinct functional properties in affinities for agonists and sensitivities to competitive antagonists and Mg2+ block. In contrast to the wide distribution of the epsilon-1 and zeta-1 subunit messenger RNAs in the brain, the epsilon-2 subunit mRNA is expressed only in the forebrain and the epsilon-3 subunit mRNA is found predominantly in the cerebellum. The epsilon-1/zeta-1 and epsilon-2/zeta-1 channels expressed in Xenopus oocytes, but not the epsilon-3/zeta-1 channel, are activated by treatment with 12-O-tetradecanoylphorbol 13-acetate. These findings suggest that the molecular diversity of the epsilon-subunit family underlies the functional heterogeneity of the NMDA receptor channel.