DQP-1105 decreases open probability of GluN1/GluN2D receptor channels
GluN1/GluN2D receptors were expressed in HEK cells and activated by glutamate (1 mM) and glycine (50 μM) in outside-out patches held under voltage clamp at −80 mV. Responses were recorded first to glutamate plus glycine (7862 open periods), and subsequently to glutamate plus glycine coapplied with 3 μM (5724 open periods) or 30 μM DQP-1105 (954 open periods) to the same patch. All values are mean ± S.E.M. (n = 4 patches). Because all patches contained multiple channels, POPEN was normalized to the value for the patch in the absence of DQP-1105 for statistical testing.
| Control | DQP-1105 | ||
|---|---|---|---|
| 3 μM | 30 μM | ||
| POPEN | 0.10 ± 0.03 | 0.038 ± 0.008 | 0.0018 ± 0.0005 |
| POPEN, % | 100 | 43 ± 12* | 2.0 ± 0.6* |
| Mean shut time, ms | 6.9 ± 1.4 | 17 ± 3* | 460 ± 130* |
| Mean open time, ms | 0.61 ± 0.03 | 0.62 ± 0.02 | 0.64 ± 0.018 |
| τ1, ms (% area) | 0.038 (31%) | 0.032 (32%) | 0.030 (42%) |
| τ2, ms (% area) | 0.62 (69%) | 0.64 (68%) | 0.65 (58%) |
| γ1, pS | 36.4 ± 1.5 | 40.8 ± 1.2* | 38 ± 2 |
| Area γ1, % | 32 ± 3 | 30. ± 6 | 26 ± 3 |
| γ2, pS | 63 ± 2 | 65 ± 2 | 65 ± 2 |
| Area γ2, % | 68 ± 3 | 70. ± 7 | 74 ± 3 |
↵* P < 0.05 versus control (one-way ANOVA with Dunnett's post test).