Functional characterization of a heteromeric NMDA receptor channel expressed from cloned cDNAs

THE glutamate receptor (GluR) channel plays a key part in brain function^1,2. Among GluR channel subtypes, the NMDA (JV-methyl-D-aspartate) receptor channel which is highly permeable to Ca ²⁺ 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 ζ1) 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 εl, after cloning and sequencing the cDNA. The ε l 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 ε I subunit together with the ζ1 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.