Fig. 2. The effects of various opioids on heteromeric NMDA receptor channels. (  A ) The current responses of the ε1/ζ1 channel before (  left ), during (  middle ), and after (  right ) perfusion of 1 mM meperidine. Inward current is downward. The duration of bath application of 10 μM L-glutamate plus 10 μM glycine is indicated by bars without taking into account the dead-space time in the perfusion system (approximately 2 s). The duration of meperidine perfusion is indicated by the  hatched column . (  B ) The dose-inhibition relationships for meperidine of four heteromeric ε/ζ channels. Each point represents the mean ± SEM of measurements on six or seven oocytes; SEMs are indicated by bars if larger than the symbols. The IC⁵⁰values (μM, mean ± SEM) of the ε1/ζ1, ε2/ζ1, ε3/ζ1, and ε4/ζ1 channels for meperidine were 233 ± 14, 206 ± 7, 264 ± 9, and 273 ± 12, respectively, and the Hill coefficient values of those were 1.00 ± 0.03, 0.99 ± 0.03, 1.14 ± 0.01, and 1.21 ± 0.02, respectively. (  C ) The dose-inhibition relationships for morphine of four heteromeric ε/ζ channels. The IC⁵⁰values (μM) of the ε1/ζ1, ε2/ζ1, ε3/ζ1, and ε4/ζ1 channels for morphine were 321 ± 48, 187 ± 9, 392 ± 27, and 650 ± 24, respectively, and the Hill coefficient values of those were 0.72 ± 0.07, 0.90 ± 0.05, 0.92 ± 0.06 and 1.01 ± 0.02, respectively (n = 6 or 7). (  D ) The effects of fentanyl, codeine and naloxone on the ε2/ζ1 channel. The IC⁵⁰values (μM) of the ε2/ζ1 channel for fentanyl, codeine, and naloxone were 192 ± 9, 613 ± 25, and 503 ± 34, respectively, and the Hill coefficient values for those were 1.18 ± 0.03, 1.32 ± 0.03, and 0.95 ± 0.02, respectively (n = 7 or 8). The control current responses (nA) of the ε1/ζ1, ε2/ζ1, ε3/ζ1, and ε4/ζ1 channels obtained before perfusion of opioids were 160–788, 165–888, 65–440, and 80–370, respectively.