GLUTATHIONE MODULATES THE N-METHYL-D-ASPARTATE RECEPTOR-ACTIVATED CALCIUM INFLUX INTO CULTURED RAT CEREBELLAR GRANULE CELLS

The effects of reduced (GSH) and oxidized (GSSG) glutathione and dithi othreitol (DTT) and L-cysteine on the influx of Ca-45(2+) were studied with cultured cerebellar granule cells. DTT slightly enhanced the bas al influx but strongly activated the influx stimulated by glutamate or N-methyl-D-aspartate (NMDA). The effects on the kainate- or quisquala te-induced influx were less pronounced. Extracellular GSH had no effec t on the basal influx of Ca2+. A concentration of 0.5 mM GSH slightly activated the glutamate- and NMDA-induced influx while GSSG was inhibi tory. The enhancement by DTT and cysteine of the responses to excitato ry amino acids was attenuated by GSH and GSSG. We propose that both th e accessibility and redox state of the functional sulfhydryl groups in NMDA receptor-ionophores may be regulated by endogenous glutathione. These effects are attributed to the gamma-glutamyl moiety and sulfhydr yl group in the tripeptide molecule.