Glycine is required for NMDA receptor activation: electrophysiological evidence from intact rat hippocampus.
Fimbrial/commissural stimulation evokes a prolonged negative field potential in stratum radiatum of CA1 region of the rat hippocampus, in situ, upon activation of N-methyl-D-aspartate (NMDA) receptors. This activity can be induced by iontophoresis of NMDLA (50 nA) or glycine (50-100 nA) during low-frequency stimulation. 7-Cl-Kynurenate (10-30 nA) fully antagonized the NMDA receptor-mediated negative wave induced not only by glycine (N = 3) but also by NMDLA (N = 9), suggesting that activation of NMDA receptors is not possible without glycine binding. 7-Cl-Kynurenate also depressed the extracellular negative d.c. potential shifts appearing during iontophoresis of NMDLA. Stimulation with brief, high-frequency trains evoked a negative wave of 2.1 +/- 0.2 mV and 176 +/- 4 ms (N = 20) on the hippocampal field response following the last stimulus. Ketamine (100-200 nA, N = 6) and MK-801 (50-200 nA, N = 7) blocked the negative wave by 74 +/- 13 and 62 +/- 8%, respectively, while glycine (100 nA) potentiated it by 35 +/- 2% (N = 6), indicating that it had a component mediated by NMDA receptors. 7-Cl-Kynurenate (100 nA) antagonized this activity at a comparable rate to the NMDA receptor antagonists (67 +/- 8%, N = 4). A similar negative wave of 0.9 +/- 0.2 mV and 41 +/- 3 ms (N = 12) was evoked in hippocampal slices by high-frequency orthodromic stimulation. Potentiation of this activity upon lowering Mg2+ in ACSF from 1.3 to 0.5 mM further supported that it had an NMDA-mediated component.(ABSTRACT TRUNCATED AT 250 WORDS)
Dalkara
T
T
Department of Neurology, University Faculty of Medicine, Ankara, Turkey.
Erdemli
G
G
Barun
S
S
Onur
R
R
D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004558:Electric Stimulation; D004594:Electrophysiology / Q000379:methods; D005071:Evoked Potentials / Q000187:drug effects; D005998:Glycine / Q000008:administration & dosage / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D007478:Iontophoresis; D007649:Ketamine / Q000494:pharmacology; D007736:Kynurenic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D016202:N-Methylaspartate / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D007649:Ketamine; D016291:Dizocilpine Maleate; D007736:Kynurenic Acid; D008274:Magnesium; C057013:7-chlorokynurenic acid; D005998:Glycine