McLarnon J, Sawyer D, Church J
Department of Pharmacology and Therapeutics, University of British Columbia, Vancouver, Canada.
Neurosci Lett. 1994 Jun 20;174(2):181-4. doi: 10.1016/0304-3940(94)90016-7.
The actions of the sigma receptor ligand L-687,384 were studied on N-methyl-D-aspartate (NMDA)-induced currents recorded from outside-out patches obtained from cultured rat hippocampal pyramidal neurons and on NMDA-evoked rises in [Ca2+]i in the same preparation. L-687,384 did not change the magnitudes of unitary NMDA currents or frequency of channel-openings but diminished channel-open probability by decreasing mean open time. This action was consistent with a voltage-dependent open-channel block of the NMDA channel by L-687,384 with a blocking rate constant of 5.9 x 10(6) M-1 s-1 at -80 mV. L-687,384 also reduced NMDA-evoked rises in [Ca2+]i in Fura-2-loaded neurons with an apparent IC50 value of 49 +/- 8 microM. The results demonstrate that L-687,384 acts as an antagonist at the NMDA receptor-channel complex.
研究了σ受体配体L-687,384对从培养的大鼠海马锥体神经元获得的外向膜片上记录的N-甲基-D-天冬氨酸（NMDA）诱导电流以及同一标本中NMDA诱发的细胞内钙离子浓度（[Ca2+]i）升高的作用。L-687,384不改变单位NMDA电流的幅度或通道开放频率，但通过缩短平均开放时间降低通道开放概率。该作用与L-687,384对NMDA通道的电压依赖性开放通道阻滞一致，在-80 mV时阻滞速率常数为5.9×10(6) M-¹ s-¹。L-687,384还降低了用Fura-2负载的神经元中NMDA诱发的[Ca2+]i升高，表观半数抑制浓度（IC50）值为49±8 μM。结果表明，L-687,384在NMDA受体-通道复合体上起拮抗剂作用。
