Selective up-regulation of an NMDA receptor subunit mRNA in cultured cerebellar granule cells by K(+)-induced depolarization and NMDA treatment.

High KCI or NMDA treatment promotes the survival of cultured neonatal cerebellar granule cells, and these cells become sensitive to NMDA toxicity after prolonged K+ depolarization. Following both treatments, the NMDA receptor increases, as assessed by fura-2 fluorescence analysis of NMDA receptor-mediated intracellular Ca2+ increase. Northern analysis indicates that both treatments specifically up-regulate NMDAR2A subunit mRNA through an increase in resting intracellular Ca2+ concentration. Antisense oligonucleotide analysis further indicates that NMDAR2A mRNA up-regulation is responsible for NMDA receptor induction. Our results demonstrate that regulation of a specific NMDA receptor subunit mRNA governs NMDA receptor induction, which is thought to play an important role in granule cell survival and death.