Table 1.
Pharmacological properties of GluN1/GluN2A/GluN2C
| Co-agonists | GluN2AC1/GluN2AC2 EC50 (95% CI) μM maximum b% | N | GluN2AC1/GluN2CC2 EC50 (95% CI) μM maximum b% | N | GluN2CC1/GluN2CC2 EC50 (95% CI) μM maximum b% | N | GluN2AC1/GluN2CC2(NKa) EC50 (95% CI) μM maximum b% | N |
|---|---|---|---|---|---|---|---|---|
| Glutamate | 2.9 (2.1, 3.7) | 14 | 1.3 (0.9, 1.7) | 11 | 0.50 (0.40, 0.60) | 10 | 0.86 (0.73, 1.0) | 8 |
| Glycine | 1.1 (0.97, 1.2) | 15 | 0.48 (0.40, 0.56) | 10 | 0.14 (0.12, 0.16) | 9 | 0.60 (0.50, 0.60) | 9 |
| DCS | 29 (22, 36) | 14 | 10 (8, 13) | 9 | 4.8 (3.9, 5.8) | 8 | 13 (11, 15) | 8 |
| Mg2+ | 26 (25, 32) | 18 | 62 (50, 79) | 11 | 200 (180, 220) | 14 | – | – |
| Zn2+ (pH 7.3) | 0.050 (0.040, 0.063) | 10 | 0.040 (0.037, 0.045) | 10 | NE | 10 | 0.045 (0.042, 0.047) | 12 |
| 57±2.0 c | 55±1.0 c | 57±0.4 c | ||||||
| Zn2+ (pH 6.8) | 0.018 (0.017, 0.020) | 13 | 0.020 (0.018, 0.028) | 14 | NE | 9 | 0.019 (0.017, 0.022) | 14 |
| 21±1.7 c | 23±1.7 c | 27±1.6 c |
The mutation N624K was introduced into GluN2CC2 (see Methods) and responses recorded in 1 mM extracellular Mg2+ to reduce leak current generated from expression of any GluN1/GluN2AC1/GluN2AC1 receptors that reach the surface, which are sensitive to Mg2+ (see Supplemental Figure S3). For Zn2+ concentration-response experiments, 0.1 mM Mg2+ was used to minimize possible effects of Mg2+ on Zn2+ binding.
The mean fitted EC50 value to 2 significant figures is given with the 95% confidence interval (CI) determined from the log EC50, followed by the mean ± SEM fitted maximal response in saturating ligand as a percent of control; no overlap in CI was considered statistically significant.
The fitted response in saturating Zn2+ agonist is given as a percent of control. – indicates no detectable effect. Hill slopes ranged from 0.6-2.8.