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 pro duced 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 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 glycin e 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 mu M zin c chloride, provided excellent protection from glycine-induced injury: 7-clorokynurenic acid appeared to be toxic. Blockers of the NMDA-asso ciated ionic channel and methyl arginine prevented loss of neural tran smission, 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 glyci ne- and glutamate-induced injury. Thus, exposure to glycine resembled the excitotoxic effects of glutamate, but showed a different profile o f protection. These results suggest that glycine elevations, as occur under physiologic and pathologic conditions, may modulate neuronal act ivity.