Glycine-induced CA1 excitotoxicity in the rat hippocampal slice.
We evaluated the effects of glycine exposure upon CA1-evoked response in the rat hippocampal slice. Exposure to 10 mM glycine for 16 min produced rapid neuronal firing and increased orthodromic population spike (PS), followed by loss of CA1 neural transmission. Upon recovery, CA1 orthodromic and antidromic PS regained a mean of only 12 +/- 6% and 8 +/- 5%, of initial amplitude. The electrophysiological pattern of glycine injury was similar to the excitotoxic damage produced by 8 min exposure to sodium glutamate (9 mM). L-Histidine, an inhibitor of glycine transport, exacerbated glycine-induced injury, just as dihydrokainic acid, a glutamate transport inhibitor, exacerbated glutamate-induced injury. The anticonvulsant felbamate (1.3 mM), as well as 100 microM zinc chloride, provided excellent protection from glycine-induced injury: 7-clorokynurenic acid appeared to be toxic. Blockers of the NMDA-associated ionic channel and methyl arginine prevented loss of neural transmission, but did not prevent accompanying hyper-excitability. Only 10 mM magnesium sulfate provided full protection against 9 mM glutamate exposure. Perfusion with low calcium ACSF protected against both glycine- and glutamate-induced injury. Thus, exposure to glycine resembled the excitotoxic effects of glutamate, but showed a different profile of protection. These results suggest that glycine elevations, as occur under physiologic and pathologic conditions, may modulate neuronal activity.
Wallis
R A
RA
Sepulveda VAMC (111N-1), CA 91343.
Panizzon
K L
KL
Nolan
J P
JP
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D004357:Drug Synergism; D005071:Evoked Potentials / Q000187:drug effects; D000078328:Felbamate; D005998:Glycine / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects*; D006639:Histidine / Q000494:pharmacology; D066298:In Vitro Techniques; D007736:Kynurenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D008278:Magnesium Sulfate / Q000494:pharmacology; D008297:Male; D048448:Phenylcarbamates; D011409:Propylene Glycols / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D017967:Zinc Compounds / Q000494:pharmacology
D000927:Anticonvulsants; D002712:Chlorides; D048448:Phenylcarbamates; D011409:Propylene Glycols; D016194:Receptors, N-Methyl-D-Aspartate; D017967:Zinc Compounds; D006639:Histidine; D008278:Magnesium Sulfate; C016837:zinc chloride; D007736:Kynurenic Acid; C057013:7-chlorokynurenic acid; D005998:Glycine; D000078328:Felbamate