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Modulation of NMDA-induced cytosolic calcium levels by ACPC in cultured cerebellar granule cells

Abstract:

The effect of 1-aminocyclopropanecarboxylic acid (ACPC) on the potentiation by glycine of N-methyl-D-aspartate (NMDA)-evoked increases in intracellular free calcium concentration [Ca2+](i) was examined in cultured rat cerebellar granule cells. NMDA (50 μM) produced a rapid and sustained increase in [Ca2+](i) from 72 ± 3 to 205 ± 18 nM. Addition of exogenous glycine potentiated (EC50 ~2 μM) the effects of NMDA, increasing [Ca2+](i) to an E(max) of 323 ± 5 nM. ACPC increased the EC50 of glycine from 2 μM (no ACPC) to 17 μM (400 μM ACPC). Concomitant with reduced potency of glycine, ACPC also inhibited the E(max) of glycine to enhance NMDA-evoked cytosolic free calcium to values (224 ± 1 nM) approaching those observed in the nominal absence of glycine. These results show that ACPC, a compound previously reported to prevent excitotoxic cell death, inhibits the glycine-induced increase of Ca2+ entry through NMDA receptors in cerebellar granule cells.