Voltage- and use-dependent block by 1-methyl-4-phenylpyridinium ion (MPP +) of N-methyl- d-aspartate-activated currents in rat hippocampal neurons

Abstract

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 μM) and picrotoxin (PTX; 50 μM) which block non-NMDA and GABA A receptors, respectively. Superfusion of MPP + reversibly decreases the pharmacologically isolated NMDA receptor-mediated excitatory postsynaptic potential (EPSPNMDA) 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 a non-competitive NMDA receptor antagonist in rat hippocampal neurons.