Anoxic LTP is mediated by the redox modulatory site of the NMDA receptor.

Abstract

1. The effects of redox reagents, 5,5'-dithiobis-2-nitrobenzoic acid (DTNB) and tris(carboxyethyl)phosphine (TCEP), on anoxia-induced long-term potentiation (LTP) were investigated in CA1 hippocampal neurons using extracellular recording techniques. Experiments were performed in the presence of 0.1 mM MgCl2 and 10 microM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) to pharmacologically isolate N-methyl-D-aspartate (NMDA) receptor-mediated responses. 2. DTNB (200 microM), a thiol oxidizing reagent, reduces by 52 +/- 9% (mean +/- SE) (n = 9/9) NMDA-receptor field potentials evoked by electrical stimulation of Schaffer collaterals and this effect could not be reversed by extensive washing. Nearly the same reduction of the initial response was obtained with different concentrations of DTNB (100 and 500 microM), but the time required to reach the maximal inhibition was concentration-dependent. 3. In keeping with an earlier study oxygen and glucose deprivation for 2-3 min induced a long-term potentiation (LTP) of the NMDA receptor response (+65 +/- 16%, n = 4/6). This potentiation was reversed by DTNB (100-500 microM) (-47 +/- 18%; n = 4/4) and the initial LTP could not be restored upon extensive washing of the drug. 4. TCEP (200 microM), a reagent which reduces S-S bond, amplified the electrically evoked NMDA-receptor EPSP (+27 +/- 12%; n = 3). In addition, TCEP (200 microM), nearly completely reversed the effect of DTNB (200 microM) on anoxia-induced LTP (+56 +/- 19%; n = 3/3). Preliminary results also indicate that TCEP occlude anoxic-LTP (n = 3/4). 5. Following DTNB (200 microM) treatment, oxygen and glucose deprivation did not generate anoxic LTP and extensive washing did not restore a potentiated NMDA field potential. 6. These observations strongly suggest that the redox site of the NMDA receptor is involved in the induction and the maintenance of the anoxic LTP of the NMDA receptor-mediated response in CA1.

• Authors: H Gozlan, D Diabira, P Chinestra, Y Ben-Ari
• Journal: Journal of neurophysiology (J Neurophysiol) Vol. 72 Issue 6 Pg. 3017-22 (Dec 1994) ISSN: 0022-3077 [Print] United States
• PMID: 7897507 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Phosphines
• Receptors, N-Methyl-D-Aspartate
• tris(2-carboxyethyl)phosphine
• 6-Cyano-7-nitroquinoxaline-2,3-dione
• Dithionitrobenzoic Acid

Topics

• 6-Cyano-7-nitroquinoxaline-2,3-dione (pharmacology)
• Animals
• Dithionitrobenzoic Acid (pharmacology)
• Electric Stimulation
• Evoked Potentials (drug effects, physiology)
• Hippocampus (cytology, physiology)
• Hypoxia, Brain (physiopathology)
• In Vitro Techniques
• Long-Term Potentiation (drug effects, physiology)
• Male
• Neurons (drug effects, physiology)
• Oxidation-Reduction
• Phosphines (pharmacology)
• Rats
• Rats, Wistar
• Receptors, N-Methyl-D-Aspartate (agonists, antagonists & inhibitors, physiology)