VOLTAGE-DEPENDENT AND USE-DEPENDENT BLOCK BY 1-METHYL-4-PHENYLPYRIDINIUM ION (MPP(-METHYL-D-ASPARTATE-ACTIVATED CURRENTS IN RAT HIPPOCAMPAL-NEURONS()) OF N)

The effects of 1-methyl-4-phenylpyridinium ion (MPP(+)) on N-methyl-D- aspartate (NMDA) receptor-channel complex were studied in rat hippocam pal neurons using intracellular- and whole-cell voltage clamp-recordin g techniques. Intracellular recordings were made from CA1 pyramidal ce lls of rat hippocampal slices in the presence of 6-cyano-7-nitroquinox aline-2,3-dione (CNQX; 10 mu M) and picrotoxin (PTX; 50 mu M) which bl ock non-NMDA and GABA(A) receptors, respectively. Superfusion of MPP() reversibly decreases the pharmacologically isolated NMDA receptor-me diated excitatory postsynaptic potential (EPSP(NMDA)) in a concentrati on-dependent manner. In other experiments, we observed that MPP(+) att enuated NMDA-evoked whole-cell currents in a voltage- and use-dependen t manner and was not dependent on the extracellular glycine or spermin e concentration on neurons freshly dissociated from rat hippocampi CA1 region. These results suggest that MPP(+), applied at micromolar conc entrations, is a non-competitive NMDA receptor antagonist in rat hippo campal neurons.