FUNCTIONAL-CHARACTERIZATION OF A HETEROMERIC NMDA RECEPTOR CHANNEL EXPRESSED FROM CLONED CDNAS

THE glutamate receptor (GluR) channel plays a kev part in brain function 1,2. Among GluR channel subtypes, the NMDA (N-methyl-D-aspartate) receptor channel which is highly permeable to Ca2+ is essential for the synaptic plasticity underlying memory, learning and development 3,4. Furthermore, abnormal activation of the NMDA receptor channel may trigger the neuronal cell death observed in various brain disorders 5,6. A complementary DNA encoding a subunit of the rodent NMDA receptor channel (NMDAR1 or zeta-1) has been cloned and its functional properties investigated 7,8. Here we report the identification and primary structure of a novel mouse NMDA receptor channel subunit, designated as epsilon-1, after cloning and sequencing the cDNA. The epsilon-1 subunit shows 11-18% amino-acid sequence identity with rodent GluR channel subunits that have been characterized so far and has structural features common to neurotransmitter-gated ion channels. Expression from cloned cDNAs of the epsilon-1 subunit together with the zeta-1 subunit in Xenopus oocytes yields functional GluR channels with high activity and characteristics of the NMDA receptor channel. Furthermore, the heteromeric NMDA receptor channel can be activated by glycine alone.