ACUTE AND CHRONIC CHANGES IN K-INDUCED DEPOLARIZATION ALTER NMDA AND NNOS GENE-EXPRESSION IN CULTURED CEREBELLAR GRANULE CELLS()

The influence of low or high (10 or 25 mM) K+-induced membrane depolar ization on the mRNA levels for NMDA receptor subunits was investigated by RNase protection assay in cultured rat cerebellar granule cells. C ells, maintained for 7 days in K-25(+), a condition that promotes thei r survival and maturation, express the highest levels of NR-1 and NR-2 A mRNA, whereas NR-2B is maximally expressed in cells grown in K-10(+) . Acute changes in medium K+ concentration had a significant effect on the mRNA levels for NMDA receptor subunits. A concomitant reduction o f NR-2A mRNA and induction of NR-2B was observed following a 24-h shif t of the culture medium from K-25(+) to K-10(+). Under these circumsta nces NR-2C, not detected in basal conditions, became expressed. Neuron al nitric oxide synthase, an enzyme linked to NMDA receptor activation , was also influenced by growth conditions. Its expression, higher und er low excitation (K-10(+)) is induced in the shift from K-25(+) to K- 10(+) and is markedly decreased in the opposite situation. These data indicate that several factors may influence the expression of NMDA rec eptor subunits and consequently may modulate the function of this rece ptor complex and its adaptation to acute and chronic changes in neuron al activity.