Dw. Newell et al., GLYCINE CAUSES INCREASED EXCITABILITY AND NEUROTOXICITY BY ACTIVATIONOF NMDA RECEPTORS IN THE HIPPOCAMPUS, Experimental neurology, 145(1), 1997, pp. 235-244
Glycine is an inhibitory neurotransmitter in the spinal cord and also
acts as a permissive cofactor required for activation of the N-methyl-
D-aspartate (NMDA) receptor. We have found that high concentrations of
glycine (10 mM) cause marked hyperexcitability and neurotoxicity in o
rganotypic hippocampal slice cultures. The hyperexcitability, measured
using intracellular recording in CA1 pyramidal neurons was completely
blocked by the NMDA receptor antagonist MK-801 (10 mu M), but not by
the AMPA receptor antagonist DNQX (100 mu M) The neurotoxicity caused
by glycine occurred in all regions of hippocampal cultures but was mos
t marked in area CA1. There was significant CA1 neuronal damage in cul
tures exposed to 10 mM glycine for 30 min or longer (P < 0.01) or thos
e exposed to 4 mM glycine for 24 h compared to control cultures (P < 0
.01). The NMDA antagonists MK-801 (10 mu M) and APV (100 mu M) signifi
cantly reduced glycine-induced neuronal damage in all hippocampal subf
ields (P < 0.01). The AMPA antagonists CNQX, DNQX, and NBQX (100 mu M)
had no effect on glycine-induced neuronal damage. High concentrations
of glycine therefore appear to enhance the excitability of hippocampa
l slices in an NMDA receptor-dependent manner. The neurotoxic actions
of glycine are also blocked by NMDA receptor antagonists. (C) 1997 Aca
demic Press.