Developmental regulation of subunit composition of extrasynaptic NMDA receptors in neocortical neurones

Neuroreport. 2000 Apr 27;11(6):1203-8. doi: 10.1097/00001756-200004270-00012.

Abstract

NMDA receptors undergo drastic changes in their subunit composition during development of the mammalian neocortex. An increase in the expression of the NR2A subunit correlates with developmental changes in the properties of synaptic NMDA receptors. In this study, we investigated whether these developmental alterations are restricted to synaptic NMDA receptors or whether similar developmental changes also occur at extrasynaptic NMDA receptors. To analyse the properties of extrasynaptic receptors, glutamate-evoked ion currents mediated by extrasynaptic NMDA receptors were isolated by irreversibly blocking synaptic NMDA receptors with MK-801. Whole-cell ion currents mediated by extrasynaptic receptors showed developmental changes in their sensitivity against the NR2B subunit-specific antagonist ifenprodil similar to that of synaptic receptors. In summary, our results strongly suggest that NR2A subunit-containing NMDA receptors increasingly contribute also to extrasynaptic NMDA receptors during in vitro differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Coculture Techniques
  • Dizocilpine Maleate / pharmacology
  • Electric Stimulation
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology
  • GABA Antagonists / pharmacology
  • Gene Expression Regulation, Developmental / drug effects
  • Gene Expression Regulation, Developmental / genetics*
  • Glutamic Acid / pharmacology
  • Glycine / pharmacology
  • Ion Channels / drug effects
  • Ion Channels / metabolism
  • Neocortex / cytology
  • Neocortex / drug effects
  • Neocortex / embryology*
  • Neocortex / metabolism*
  • Neurons / cytology
  • Neurons / metabolism*
  • Patch-Clamp Techniques
  • Picrotoxin / pharmacology
  • Piperidines / pharmacology
  • Quinoxalines / pharmacology
  • Rats
  • Rats, Wistar
  • Receptors, AMPA / antagonists & inhibitors
  • Receptors, N-Methyl-D-Aspartate / genetics
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Stimulation, Chemical
  • Synapses / drug effects

Substances

  • Excitatory Amino Acid Antagonists
  • GABA Antagonists
  • Ion Channels
  • Piperidines
  • Quinoxalines
  • Receptors, AMPA
  • Receptors, N-Methyl-D-Aspartate
  • Picrotoxin
  • Glutamic Acid
  • FG 9041
  • Dizocilpine Maleate
  • ifenprodil
  • Glycine