AMPA glutamate receptor-mediated calcium signaling is transiently enhanced during development of oligodendrocytes

J Neurochem. 2002 Apr;81(2):390-402. doi: 10.1046/j.1471-4159.2002.00866.x.


Cells of the oligodendroglial lineage express Ca2+-permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate-preferring glutamate receptors (AMPA-GluR) during development. Prolonged activation of their AMPA-GluR causes Ca2+ overload, resulting in excitotoxic death. Prior studies have shown that oligodendroglial progenitors and immature oligodendrocytes are susceptible to excitotoxicity, whereas mature oligodendrocytes are resistant. An unresolved issue has been why Ca2+-permeability of AMPA-GluR varies so markedly with oligodendroglial development, although the level of expression of edited GluR2, an AMPA-GluR subunit which blocks Ca2+ entry, is relatively constant. To address this question, we performed Ca2+ imaging, molecular and electrophysiological analyses using purified cultures of the rat oligodendroglial lineage. We demonstrate that transient up-regulation of expression of GluR3 and GluR4 subunits in oligodendroglial progenitors and immature oligodendrocytes results in the assembly by these cells, but not by oligodendroglial pre-progenitors or mature oligodendrocytes, of a population of AMPA-GluR which lack GluR2. This stage-specific up-regulation of edited GluR2-free, and hence Ca2+-permeable, AMPA-GluR explains the selective susceptibility to excitotoxicity of cells at these stages of oligodendroglial differentiation, and is likely to be important to these cells in the trans-synaptic Ca2+-signaling from glutamatergic neurons, which occurs in hippocampus

Publication types

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

MeSH terms

  • Animals
  • Calcium / metabolism
  • Calcium Signaling / physiology*
  • Cell Differentiation / physiology
  • Cell Lineage
  • Cells, Cultured
  • Electric Capacitance
  • Fluorescent Dyes
  • Immunohistochemistry
  • Intracellular Fluid / metabolism
  • Membrane Potentials / physiology
  • Oligodendroglia / cytology
  • Oligodendroglia / metabolism*
  • Patch-Clamp Techniques
  • Protein Subunits
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, AMPA / genetics
  • Receptors, AMPA / metabolism*
  • Receptors, Glutamate / genetics
  • Receptors, Glutamate / metabolism*
  • Time Factors
  • Up-Regulation / physiology


  • Fluorescent Dyes
  • Protein Subunits
  • RNA, Messenger
  • Receptors, AMPA
  • Receptors, Glutamate
  • glutamate receptor ionotropic, AMPA 3
  • glutamate receptor ionotropic, AMPA 4
  • glutamate receptor ionotropic, AMPA 2
  • Calcium
  • glutamate receptor ionotropic, AMPA 1