FUNCTIONAL CONSEQUENCES OF NR2 SUBUNIT COMPOSITION IN SINGLE RECOMBINANT N-METHYL-D-ASPARTATE RECEPTORS

Single-channel recordings were obtained from Chinese hamster ovary cel ls transfected with the N-methyl-D-aspartate (NMDA) receptor subunit N R1 in combination with NR2A, NR2B, NR2C, or NR2A/NR2B. NMDA-activated currents were recorded under control conditions and in the presence of a thiol reductant (DTT), an oxidant (5,5'-dithio-bis [2-nitrobenzoic acid], DTNB), or the noncompetitive antagonist CP101,606 (CP). For all subunit combinations, DTT increased the frequency of channel opening when compared with DTNB. In addition, channels obtained from NR1/NR2A- transfected cells also exhibited a pronounced difference in mean open dwell-time between redox conditions. CP dramatically reduced both the open dwell-time and frequency of channel opening of NR1/NR2B-containin g receptors, but only modestly inhibited NR1/NR2A and NR1/NR2C channel activity. A small number of patches obtained from cells transfected w ith NR1/NR2A/NR2B had channels with properties intermediate to NR1/NR2 A and NR1/NR2B receptors, including insensitivity to CP block but redo x properties similar to NR1/NR2B, consistent with the coassembly of NR 2A with NR2B, Hence, NMDA receptors containing multiple types of NR2 s ubunits can have functionally distinguishable attributes.