GLYCINE IS REQUIRED FOR NMDA RECEPTOR ACTIVATION - ELECTROPHYSIOLOGICAL EVIDENCE FROM INTACT RAT HIPPOCAMPUS

DALKARA T., ERDEMLI G., BARUN S., ONUR R.

BRAIN RESEARCH, cilt.576, sa.2, ss.197-202, 1992 (SCI-Expanded) identifier identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 576 Sayı: 2
  • Basım Tarihi: 1992
  • Doi Numarası: 10.1016/0006-8993(92)90680-8
  • Dergi Adı: BRAIN RESEARCH
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.197-202
  • Anahtar Kelimeler: 7-CL-KYNURENATE, GLUTAMATE, N-METHYL-D-ASPARTATE, GLYCINE, HIPPOCAMPUS, METHYL-D-ASPARTATE, SPINAL-CORD NEURONS, 7-CHLOROKYNURENIC ACID, SYNAPTIC TRANSMISSION, MODULATORY SITE, CHANNEL COMPLEX, MOUSE, ANTAGONISTS, INDUCTION, RESPONSES
  • Gazi Üniversitesi Adresli: Hayır

Özet

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. The negative wave was depressed by iontophoresis of MK-801 (34 +/- 1%, N = 2) and 7-Cl-kynurenate (39 +/- 12%, N = 5). Perfusion with 7-Cl-kynurenate (10-30-mu-M, N = 4), MK-801 (100-mu-M, N = 3) and 2.6 mM Mg2+ (N = 3) also inhibited this wave by 47 +/- 14, 32 +/- 15 and 54 +/- 5%, respectively. Antagonism by 7-Cl-kynurenate of the part of the hippocampal field potential sensitive to NMDA receptor antagonists suggests that binding of endogenous glycine to the NMDA receptor is required for NMDA receptor activation