POTENTIATION OF N-METHYL-D-ASPARTATE-EVOKED ELEVATION OF INTRACELLULAR CA2+ CONCENTRATIONS BY EXOGENOUS GLYCINE IN CEREBELLAR GRANULE CELLS

The effect of glycine on the intracellular free Ca2+ concentration ([C a2+])(i) response to N-methyl-D-aspartate (NMDA) was examined in small groups of cerebellar granule cells loaded with fura 2. NMDA alone evo ked a long-lasting monophasic [Ca2+](i) plateau, which was abolished b y removal of extracellular Ca2+, or addition of the NMDA channel antag onist dizocilpine or the glycine site antagonist 5,7-dichlorokynurenic acid, virtually unaffected by the L-type Ca2+ channel antagonist (-)- PN 202 791, and greatly, though variably, potentiated by addition of g lycine. In the presence of glycine the response to NMDA was clearly bi phasic. However, there was no consistent relationship between the magn itudes of the peak and plateau phases of the response, and their tempo ral relationship was also highly variable. The potentiation seen with exogenous glycine was highly dependent on plating density, which may b e the result of higher levels of endogenous glycine in more dense cult ures. Our results provide an explanation of the inconsistent findings previously reported by different groups on the potentiation of the [Ca 2+](i) response to NMDA by exogenous glycine.