Hsu K S, Huang C C, Gean P W
Department of Pharmacology, College of Medicine, National Cheng-Kung University, Tainan, Taiwan.
Neurosci Lett. 1995 Apr 7;189(1):17-20. doi: 10.1016/0304-3940(95)11438-3.
The effects of 1-methyl-4-phenylpyridinium ion (MPP+) on N-methyl-D-aspartate (NMDA) receptor-channel complex were studied in rat hippocampal neurons using intracellular- and whole-cell voltage clamp-recording techniques. Intracellular recordings were made from CA1 pyramidal cells of rat hippocampal slices in the presence of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 10 microM) and picrotoxin (PTX; 50 microM) which block non-NMDA and GABA receptors, respectively. Superfusion of of MPP+ reversibly decreases the pharmacologically isolated NMDA receptor-mediated excitatory postsynaptic potential (EPSP(NMDA)) in a concentration-dependent manner. In other experiments, we observed that MPP+ attenuated NMDA-evoked whole-cell currents in a voltage- and use-dependent manner and was not dependent on the extracellular glycine or spermine concentration on neurons freshly dissociated from rat hippocampi CA1 region. These results suggest that MPP+ applied at micromolar concentrations, is non-competitive NMDA receptor antagonist in rat hippocampal neurons.
采用细胞内和全细胞电压钳记录技术，在大鼠海马神经元中研究了1-甲基-4-苯基吡啶离子（MPP+）对N-甲基-D-天冬氨酸（NMDA）受体通道复合物的影响。在分别阻断非NMDA和GABA受体的6-氰基-7-硝基喹喔啉-2,3-二酮（CNQX；10微摩尔）和苦味毒（PTX；50微摩尔）存在的情况下，从大鼠海马切片的CA1锥体细胞进行细胞内记录。MPP+的灌流以浓度依赖性方式可逆地降低药理学分离的NMDA受体介导的兴奋性突触后电位（EPSP(NMDA)）。在其他实验中，我们观察到MPP+以电压和使用依赖性方式减弱NMDA诱发的全细胞电流，并且不依赖于从大鼠海马CA1区新鲜分离的神经元的细胞外甘氨酸或精胺浓度。这些结果表明，以微摩尔浓度应用的MPP+是大鼠海马神经元中的非竞争性NMDA受体拮抗剂。
