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

Neurosci Lett. 1995 Apr 7;189(1):17-20. doi: 10.1016/0304-3940(95)11438-3.

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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenylpyridinium / pharmacology*
  • 6-Cyano-7-nitroquinoxaline-2,3-dione / pharmacology
  • Animals
  • Electrophysiology
  • Hippocampus / cytology
  • Hippocampus / drug effects
  • Hippocampus / physiology*
  • Ion Channels / antagonists & inhibitors*
  • Ion Channels / drug effects
  • Ion Channels / physiology
  • Ions
  • Male
  • Neurons / drug effects
  • Neurons / physiology*
  • Picrotoxin / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*
  • Receptors, N-Methyl-D-Aspartate / drug effects
  • Receptors, N-Methyl-D-Aspartate / physiology
  • Synaptic Transmission / drug effects

Substances

  • Ion Channels
  • Ions
  • Receptors, N-Methyl-D-Aspartate
  • Picrotoxin
  • 6-Cyano-7-nitroquinoxaline-2,3-dione
  • 1-Methyl-4-phenylpyridinium