Developmental switch in the expression of NMDA receptors occurs in vivo and in vitro

Neuron. 1993 Feb;10(2):267-78. doi: 10.1016/0896-6273(93)90317-k.


The properties of many ligand-gated ion channels are altered during development. We have characterized a developmental switch in the sensitivity of NMDA receptors to the novel antagonist ifenprodil using ligand binding assays with rat brain membranes and voltage-clamp recording of Xenopus oocytes expressing NMDA receptors after injection of RNA from rat brain and from cloned subunits of the receptor. In neonatal rat brain, NMDA receptors have a uniformly high affinity for ifenprodil. During postnatal development, a second population of receptors having a 100-fold lower affinity for ifenprodil is expressed and represents 50% of NMDA receptors in adult rat brain. This developmental change also occurred in cortical neurons maintained in primary culture. Ifenprodil potently inhibited responses of homomeric NR1 and heteromeric NR1/NR2B receptors but not NR1/NR2A receptors expressed in oocytes, suggesting that inclusion of different NR2 subunits in native NMDA receptors can control the sensitivity to ifenprodil.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Animals, Newborn / metabolism
  • Brain / embryology
  • Brain / growth & development*
  • Brain / metabolism
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Cells, Cultured
  • Cerebral Cortex / growth & development
  • Cerebral Cortex / metabolism
  • Cloning, Molecular
  • Dizocilpine Maleate / metabolism
  • Female
  • Gene Expression
  • Neurons / drug effects
  • Neurons / metabolism
  • Oocytes / metabolism
  • Piperidines / metabolism
  • Piperidines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Receptors, N-Methyl-D-Aspartate / genetics
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Transfection
  • Xenopus laevis


  • Piperidines
  • Receptors, N-Methyl-D-Aspartate
  • Dizocilpine Maleate
  • ifenprodil