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

• Published in: Journal of neurochemistry 2002-04, Vol.81 (2), p.390-402
• Main Authors: Itoh, Takayuki, Beesley, Jacqueline, Itoh, Aki, Cohen, Akiva S., Kavanaugh, Bryan, Coulter, Douglas A., Grinspan, Judith B., Pleasure, David
• Format: Article
• Language: English
• Subjects: AMPA receptor; Animals; Biological and medical sciences; calcium; Calcium - metabolism; Calcium Signaling - physiology; Cell Differentiation - physiology; Cell Lineage; Cells, Cultured; Electric Capacitance; electrophysiology; Fluorescent Dyes; Fundamental and applied biological sciences. Psychology; fura‐2 microfluorometry; Immunohistochemistry; Intracellular Fluid - metabolism; Isolated neuron and nerve. Neuroglia; Membrane Potentials - physiology; Oligodendroglia - cytology; Oligodendroglia - metabolism; oligodendroglial lineage; Patch-Clamp Techniques; Protein Subunits; Rats; Rats, Sprague-Dawley; Receptors, AMPA - genetics; Receptors, AMPA - metabolism; Receptors, Glutamate - genetics; Receptors, Glutamate - metabolism; RNA, Messenger - metabolism; Time Factors; Up-Regulation - physiology; Vertebrates: nervous system and sense organs
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1046/j.1471-4159.2002.00866.x

Cells of the oligodendroglial lineage express Ca2+‐permeable α‐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 in vivo.