MOLECULAR-CLONING, FUNCTIONAL EXPRESSION, AND PHARMACOLOGICAL CHARACTERIZATION OF AN N-METHYL-D-ASPARTATE RECEPTOR SUBUNIT FROM HUMAN BRAIN

A cDNA encoding a full-length N-methyl-D-aspartate (NMDA) receptor sub unit 1, hNR1, was isolated from a human brain cDNA library. The hNR1 c DNA encodes an open reading frame of almost-equal-to 2.7 kb that share s high homology with the rat brain NMDA receptor subunit 1 and the mou se zeta1 subunit. The hNR1 sequence, however, diverges from the rodent and murine homologs near the C terminus, suggesting that they represe nt alternatively spliced messages of the same gene. Oocytes injected w ith cRNA synthesized from the hNR1 cDNA express glutamate and NMDA-act ivated currents in the presence of glycine. Currents are blocked by th e NMDA-receptor-specific antagonists 2-amino-5-phosphovaleric acid and 7-chlorokynurenate, and the open channel blockers MK-801 and phencycl idine, by Mg2+ ions in a voltage-dependent manner, and by Zn2+. Expres sed hNR1 homomeric receptor channels exhibit the high Ca2+ permeabilit y characteristic of neuronal NMDA receptors. Therefore, the cDNA clone hNR1 codes for a human brain NMDA receptor subunit cognate to the rod ent and murine brain NR1 subunits.