Voltage- and use-dependent block by 1-methyl-4-phenylpyridinium ion (MPP+) of N-methyl-D-aspartate-activated currents in rat hippocampal neurons.
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.
Hsu
K S
KS
Department of Pharmacology, College of Medicine, National Cheng-Kung University, Tainan, Taiwan.
Huang
C C
CC
Gean
P W
PW
D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology*; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D004594:Electrophysiology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D007473:Ion Channels / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000502:physiology; D007477:Ions; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects
D015655:1-Methyl-4-phenylpyridinium; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D007473:Ion Channels; D007477:Ions; D010852:Picrotoxin; D016194:Receptors, N-Methyl-D-Aspartate