Inhibition of NMDA receptors by EU93-108. (A) Current response
time course for maximal receptor activation by 100 μM l-glutamate and 100 μM glycine (GG) and then in the continuous
presence of 100 μM l-glutamate and glycine plus increasing
concentrations of EU93-108 at 0.03, 0.1, 0.3, 1, 3, and 10 μM
is shown for each receptor subunit combination. The receptors tested
are diheteromeric rat GluN1/GluN2Ac1/GluN2Ac2 (r2Ac1/r2Ac2), triheteromeric
rat GluN1/GluN2Ac1/GluN2Bc2 (r2Ac1/r2Bc2), diheteromeric rat GluN1/GluN2Bc1/GluN2Bc2
(r2Bc1/r2Bc2), and diheteromeric human GluN1/GluN2B/GluN2B (h2B/h2B).
All currents were normalized to the maximal response in 100 μM
glutamate and glycine, set as 100%. The mean ± SEM for maximal
current sizes for r2Ac1/r2Ac2 receptors was 295 ± 44 nA (n = 6), for r2Ac1/r2Bc2 receptors 278 ± 39 nA (n = 12), for r2Bc1/r2Bc2 receptors 353 ± 77 nA (n = 8), and for h2B/h2B receptors 276 ± 63 nA (n = 10). (B) Concentration–effect curve for inhibition
by EU93-108 for all four receptor subunit combinations, with the same
symbols as in (A). The mean ± SEM values are plotted for r2Ac1/r2Ac2
receptors (open triangles, n = 6), r2Ac1/r2Bc2 receptors
(closed circles, n = 12), r2Bc1/r2Bc2 receptors (open
circles, n = 8), and h2B/h2B receptors (open squares, n = 10) with increasing concentrations of EU93-108 applied
in the presence of 100 μM glutamate and 100 μM glycine
at −40 mV as described in the Materials and
Methods section.