Nitric oxide modulates synaptic glutamate release during anoxia.
The ability of nitric oxide to enhance vesicular glutamate release during anoxia was examined in the present study. Whole-cell patch clamp recordings were obtained from CA1 pyramidal neurons in rat hippocampal slices perfused in media containing tetrodotoxin. These cells exhibit spontaneous inward currents previously identified as glutamatergic miniature excitatory postsynaptic currents (mEPSCs). The frequency of these mEPSCs increases during exposure to anoxia. The anoxia-induced increase in frequency is reduced when experiments are performed in the presence of the competitive nitric oxide (NO)-synthase inhibitors N(G)-nitro-L-arginine methyl ester and N(G)-nitro-L-arginine, as well as reduced hemoglobin. Arginine reversed the suppression by the NO-synthase inhibitors. The N-methyl-D-aspartate (NMDA) receptor antagonists 3-(2-carboxypiperazine-4-yl)propyl-1-phosphonic acid and MK-801 also suppressed the anoxia-induced increase in mEPSC frequency. These data indicate that NMDA receptor-activated NO production may enhance vesicular synaptic glutamate release, which would in turn contribute to excitotoxicity during hypometabolic states.
Katchman
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AN
Department of Neurology, Georgetown University Medical Center, Washington, DC 20007, USA.
Hershkowitz
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N
D000818:Animals; D004553:Electric Conductivity; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D000860:Hypoxia / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D066298:In Vitro Techniques; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000378:metabolism* / Q000502:physiology
D004791:Enzyme Inhibitors; D019335:Nitroarginine; D009569:Nitric Oxide; D018698:Glutamic Acid; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester