Table 4.
pH dependence of MK-801 potency in native NMDA receptors
| (+)MK-801 | (−)MK-801 | |||||
|---|---|---|---|---|---|---|
| Assay | IC50 (nm) pH 7.6 | IC50 (nm) pH 6.9 | IC50 ratio 7.6/6.9 | IC50 (nm) pH 7.6 | IC50 (nm) pH 6.9 | IC50 ratio 7.6/6.9 |
| [Ca2+]i | 80 ± 13 | 21 ± 13 | 3.6 | 524 ± 157 | 90 ± 13 | 5.8 |
| LDH efflux | 35 ± 15 | 39 ± 14 | 0.9 | 580 ± 123 | 75 ± 13 | 7.7 |
A pH-dependent shift in the potency of MK-801 isomers is evident in native mouse NMDA receptors. Intracellular calcium was monitored using the Ca2+-sensitive dye fluo-3 AM in neocortical neurons. Cell death was measured using the LDH efflux assay in neocortical neurons at two different pH values. Values of IC50 were obtained from non-linear least-squares fitting of the concentration–response curves shown in Fig. 5. Data are averaged from 3–6 measurements in 2 experiments. The NMDA receptors were activated by 50 μm glutamate and 50 μm glycine.