TABLE 2.
The structural determinants of ifenprodil inhibition
Fitted IC50 values are shown to two significant figures and were determined from composite concentration-effect curves constructed from recordings in 8 to 41 oocytes (n) as described under Materials and Methods; the steady-state response was fixed at 0 for all conditions except GluN2B wild type. The following GluN2B mutations had less than 1.5-fold effect on the ifenprodil IC50 value: I50A, K51A, H127A, Q153A, Q180R, C232A, V258A, W285A, R328P (n = 4–20 oocytes per mutant). The ratio of IC50 values compared with control run during the same experiment.
| GluN2B mutation | IC50 | IC50 Mutant/IC50 Wild Type | n |
|---|---|---|---|
| μM | |||
| Wild type | 0.10 | 41 | |
| D101Aa | 47 | 246 | 8 |
| D102Aa | 0.34 | 1.8 | 8 |
| Q110A | 0.90 | 9.0 | 11 |
| Q110E | 0.039 | 0.39 | 25 |
| L205A | 0.28 | 2.8 | 14 |
| G212A,D213K | 2.1 | 21 | 20 |
| D213A | 0.79 | 7.9 | 14 |
| Y231A | 60 | 598 | 18 |
| T233Aa | 8.1 | 43 | 9 |
| T233S | 3.3 | 33 | 15 |
| S281A | 0.22 | 2.2 | 14 |
| Y282A | 12 | 121 | 23 |
| I299A | 0.28 | 2.8 | 14 |
Data are from mouse GluN2B coexpressed with rat GluN1, and IC50 values for ifenprodil were compared with IC50 from wild-type mouse GluN2B (0.19 μM). All other data are from rat GluN1/GluN2B receptors.