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

Neuron. 1994 Jan;12(1):87-95. doi: 10.1016/0896-6273(94)90154-6.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Base Sequence
  • Blotting, Northern
  • Cells, Cultured
  • Cerebellum / cytology
  • Cerebellum / metabolism*
  • Gene Expression / drug effects
  • Gene Expression / physiology*
  • Macromolecular Substances
  • Molecular Sequence Data
  • N-Methylaspartate / pharmacology*
  • N-Methylaspartate / toxicity
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism*
  • Oligonucleotides, Antisense
  • Potassium / pharmacology*
  • RNA, Messenger / biosynthesis*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate / biosynthesis*
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Transcription, Genetic / drug effects
  • Transcription, Genetic / physiology
  • Up-Regulation / drug effects


  • Macromolecular Substances
  • Oligonucleotides, Antisense
  • RNA, Messenger
  • Receptors, N-Methyl-D-Aspartate
  • N-Methylaspartate
  • Potassium