Lerma J, Zukin R S, Bennett M V
Instituto de Neurobiologia S. Ramon y Cajal, Consejo Superior de Investigaciones Cientificas, Madrid, Spain.
Neurosci Lett. 1991 Feb 25;123(2):187-91. doi: 10.1016/0304-3940(91)90927-l.
The interaction between Mg2+ and phencyclidine (PCP) in blocking open N-methyl-D-aspartate (NMDA) channels was investigated in Xenopus oocytes injected with rat brain mRNA. These receptors exhibit the pharmacological and physiological properties of the neuronal receptors, and the oocyte is readily amenable to electrical recording and application of well-controlled chemical stimuli. We found that Mg2+ at physiological concentrations greatly impeded the ability of PCP to block the NMDA channel. The interaction between Mg2+ and PCP was competitive; 0.5 mM Mg2+ caused a four-fold decrease in the potency of PCP in blocking open NMDA channels. Moreover, Mg2+ speeded the recovery from PCP block in the presence of agonist, suggesting that Mg2+ reduced reblock of NMDA channels by PCP that had escaped from open channels. Our observations suggest that the presence of Mg2+ in the channel tends to prevent PCP entry and block. Since depolarization is likely to reduce channel occupancy by Mg2+ more than that by PCP, neural activity may have an important influence on the actions of PCP and related drugs.
在注射了大鼠脑信使核糖核酸（mRNA）的非洲爪蟾卵母细胞中，研究了镁离子（Mg2+）与苯环己哌啶（PCP）在阻断开放的N-甲基-D-天冬氨酸（NMDA）通道方面的相互作用。这些受体展现出神经元受体的药理学和生理学特性，并且卵母细胞易于进行电记录以及施加控制良好的化学刺激。我们发现，生理浓度的Mg2+极大地阻碍了PCP阻断NMDA通道的能力。Mg2+与PCP之间的相互作用是竞争性的；0.5 mM Mg2+使PCP阻断开放NMDA通道的效力降低了四倍。此外，在存在激动剂的情况下，Mg2+加快了从PCP阻断状态的恢复，这表明Mg2+减少了已从开放通道逸出的PCP对NMDA通道的再次阻断。我们的观察结果表明，通道中Mg2+的存在倾向于阻止PCP进入并阻断通道。由于去极化可能比PCP更能减少通道被Mg2+占据的情况，神经活动可能对PCP及相关药物的作用有重要影响。
