GLYCINE-INDUCED CA1 EXCITOTOXICITY IN THE RAT HIPPOCAMPAL SLICE (VOL 664, PG 115, 1994)

We evaluated the effects of glycine exposure upon CA1 evoked response in the rat hippocampal slice. Exposure to 10 mM glycine for 16 min, pr oduced rapid neuronal firing and increased orthodromic population spik e (PS), followed by loss of CA1 neural transmission. Upon recovery, CA 1 orthodromic and antidromic PS regained a mean of only 12 +/- 6% and 8 +/- 5% of initial amplitude. The electrophysiological pattern of gly cine injury was similar to the excitotoxic damage produced by 8 min ex posure to sodium glutamate 9 mM. L-Histidine, an inhibitor of glycine transport, exacerbated glycine-induced injury, just as dihydrokainic a cid, a glutamate transport inhibitor, exacerbated glutamate-induced in jury. The anticonvulsant felbamate (1.3 mM), as well as 100 mu M zinc chloride, provided excellent protection from glycine-induced injury. 7 -Chlorokynurenic acid appeared to be toxic. Blockers of the NMDA-assoc iated ionic channel and methyl arginine, prevented loss of neural tran smission, but did not prevent accompanying hyperexcitability. Only 10 mM magnesium sulfate provided full protection against 9 mM glutamate e xposure. Perfusion with low calcium ACSF protected against both glycin e and glutamate-induced injury. Thus, exposure to glycine resembled th e excitotoxic effects of glutamate, but showed a different profile of protection. These results suggest that glycine elevations as occur und er physiologic and pathologic conditions may modulate neuronal activit y.