Table 3.
Channel block of diheteromeric and triheteromeric NMDA receptor subtypes.
| GluN1–1a/2B | GluN1–1a/2BC1/2DC2 | GluN1–1a/2D | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Ligand | Holding potential (mV) | IC50 (μM) or IC50 ratio | nH | n | IC50 (μM) or IC50 ratio | nH | n | IC50 (μM) or IC50 ratio | nH | n |
| Mg2+ | −40 | 161.1 ± 11.8 | 0.9 | 8 | 518.4 ± 14.3*,# | 0.8 | 5 | 936.7 ± 85.9 | 1.0 | 4 |
| Mg2+ | −60 | 25.5 ± 1.5 | 1.0 | 8 | 79.2 ± 3.0*,# | 0.9 | 5 | 253.7 ± 10.9 | 1.0 | 4 |
| Mg2+ | −80 | 5.5 ± 0.4 | 1.0 | 8 | 19.9 ± 0.8*,# | 0.9 | 5 | 72.5 ± 1.8 | 1.0 | 4 |
| Mg2+ | −100 | 1.6 ± 0.3 | 0.9 | 8 | 6.8 ± 0.5*,# | 0.9 | 5 | 25.1 ± 0.4 | 1.0 | 4 |
| memantine (control) | −20 | 2.7 ± 0.2 | 0.9 | 6 | 2.5 ± 0.4# | 1.1 | 4 | 1.1 ± 0.1 | 1.1 | 6 |
| memantine (+ Mg2+) | −20 | 9.5 ± 0.6 | 1.1 | 6 | 3.2 ± 0.1*,# | 1.0 | 6 | 1.4 ± 0.1 | 1.0 | 6 |
| IC50 ratio (Mg2+/control) | −20 | 3.5 | 1.3 | 1.3 | ||||||
| memantine (control) | −40 | 1.3 ± 0.1 | 1.0 | 6 | 1.2 ± 0.1# | 1.0 | 4 | 0.7 ± 0.0 | 1.1 | 6 |
| memantine (+ Mg2+) | −40 | 12.0 ± 2.0 | 1.0 | 6 | 2.6 ± 0.2*,# | 0.9 | 6 | 1.0 ± 0.0 | 1.0 | 6 |
| IC50 ratio (Mg2+/control) | −40 | 9.2 | 2.2 | 1.4 | ||||||
| memantine (control) | −60 | 0.6 ± 0.0 | 1.0 | 6 | 0.6 ± 0.0# | 1.0 | 4 | 0.4 ± 0.0 | 1.1 | 6 |
| memantine (+ Mg2+) | −60 | 8.9 ± 1.5 | 1.1 | 5 | 2.6 ± 0.3*,# | 0.9 | 4 | 0.8 ± 0.0 | 1.0 | 6 |
| IC50 ratio (Mg2+/control) | −60 | 14.8 | 4.3 | 2.0 | ||||||
| ketamine (control) | −20 | 4.2 ± 0.7 | 1.0 | 6 | 3.9 ± 0.2 | 1.0 | 6 | 3.8 ± 0.2 | 1.0 | 6 |
| ketamine (+ Mg2+) | −20 | 16.3 ± 1.9 | 1.2 | 6 | 7.6 ± 0.5*,# | 1.1 | 6 | 4.5 ± 0.5 | 1.0 | 6 |
| IC50 ratio (Mg2+/control) | −20 | 3.9 | 1.9 | 1.2 | ||||||
| ketamine (control) | −40 | 2.1 ± 0.3 | 1.0 | 6 | 2.1 ± 0.1 | 1.0 | 6 | 2.4 ± 0.2 | 1.0 | 6 |
| ketamine (+ Mg2+) | −40 | 19.2 ± 2.0 | 1.3 | 6 | 6.7 ± 0.6*,# | 1.1 | 6 | 3.5 ± 0.5 | 1.0 | 6 |
| IC50 ratio (Mg2+/control) | −40 | 9.1 | 3.2 | 1.5 | ||||||
| ketamine (control) | −60 | 1.0 ± 0.1 | 1.0 | 6 | 1.1 ± 0.1 | 1.1 | 6 | 1.3 ± 0.1 | 1.0 | 6 |
| ketamine (+ Mg2+) | −60 | 17.0 ± 2.0 | 1.1 | 5 | 5.7 ± 0.8*,# | 1.2 | 6 | 2.6 ± 0.4 | 1.1 | 6 |
| IC50 ratio (Mg2+/control) | −60 | 17.0 | 5.2 | 2.0 | ||||||
Channel block of NMDA receptor responses to 300 μM glutamate plus 100 μM glycine was measured using two-electrode voltage-clamp recordings of responses from NMDA receptors. Memantine and ketamine block was evaluated in the absence (control) and presence of 1 mM Mg2+. Maximal inhibition was fixed to 100% during data analysis. Data are mean ± SEM, and n is the number of oocytes used to generate the data. Statistical analyses were performed using logIC50 values.
*
indicates significantly different from GluN1/2B (P < 0.05) and
#
indicates significantly different from GluN1/2D (P < 0.05) using one-way ANOVA with Tukey’s post hoc test.