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.
Bessho
Y
Y
Institute for Immunology, Kyoto University, Faculty of Medicine, Japan.
Nawa
H
H
Nakanishi
S
S
D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D015152:Blotting, Northern; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology*; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D016202:N-Methylaspartate / Q000494:pharmacology* / Q000633:toxicity; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016376:Oligonucleotides, Antisense; D011188:Potassium / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis* / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects
D046911:Macromolecular Substances; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D011188:Potassium