Regulation of glutamate transport in developing rat oligodendrocytes.
Glutamate released from synaptic vesicles mediates excitatory neurotransmission by stimulating glutamate receptors. Glutamate transporters maintain low synaptic glutamate levels critical for this process, a role primarily attributed to astrocytes. Recently, vesicular release of glutamate from unmyelinated axons in the rat corpus callosum has been shown to elicit AMPA receptor-mediated currents in glial progenitor cells. Glutamate transporters are the only mechanism of glutamate clearance, yet very little is known about the role of glutamate transporters in normal development of oligodendrocytes (OLs) or in excitotoxic injury to OLs. We found that OLs in culture are capable of sodium-dependent glutamate uptake with a K(m) of 10 +/- 2 microm and a V(max) of 2.6, 5.0, and 3.8 nmol x min(-1) x mg(-1) for preoligodendrocytes, immature, and mature OLs, respectively. Surprisingly, EAAC1, thought to be exclusively a neuronal transporter, contributes more to [(3)H]l-glutamate uptake in OLs than GLT1 or GLAST. These data suggest that glutamate transporters on oligodendrocytes may serve a critical role in maintaining glutamate homeostasis at a time when unmyelinated callosal axons are engaging in glutamatergic signaling with glial progenitors. Furthermore, GLT1 was significantly increased in cultured mature OLs contrary to in vivo data in which we have shown that, although GLT1 is present on developing OLs when unmyelinated axons are prevalent in the developing rat corpus callosum, after myelination, GLT1 is not expressed on mature OLs. The absence of GLT1 in mature OLs in the rat corpus callosum and its presence in mature rat cultured OLs may indicate that a signaling process in vivo is not activated in vitro.
DeSilva
Tara M
TM
Department of Neurology and F. M. Kirby Neurobiology Center, Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Kabakov
Anatoli Y
AY
Goldhoff
Patricia E
PE
Volpe
Joseph J
JJ
Rosenberg
Paul A
PA
D000818:Animals; D000831:Animals, Newborn; D001224:Aspartic Acid / Q000494:pharmacology; D001569:Benzodiazepines / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D001921:Brain / Q000166:cytology* / Q000254:growth & development*; D002478:Cells, Cultured; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D027342:Excitatory Amino Acid Transporter 2 / Q000037:antagonists & inhibitors / Q000502:physiology*; D050580:Excitatory Amino Acid Transporter 3 / Q000037:antagonists & inhibitors / Q000502:physiology*; D005260:Female; D005346:Fibroblast Growth Factors / Q000378:metabolism; D018756:GABA Antagonists / Q000494:pharmacology; D005732:Gangliosides / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology*; D018698:Glutamic Acid / Q000378:metabolism*; D007608:Kainic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000378:metabolism; D019081:O Antigens / Q000378:metabolism; D009836:Oligodendroglia / Q000378:metabolism*; D018408:Patch-Clamp Techniques / Q000379:methods; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D011247:Pregnancy; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D014316:Tritium / Q000378:metabolism
D018691:Excitatory Amino Acid Antagonists; D027342:Excitatory Amino Acid Transporter 2; D050580:Excitatory Amino Acid Transporter 3; D018756:GABA Antagonists; D005732:Gangliosides; D019081:O Antigens; D010982:Platelet-Derived Growth Factor; D011810:Quinoxalines; C493398:Slc1a1 protein, rat; D026941:Sodium Channel Blockers; C120673:benzyloxyaspartate; C062875:ganglioside A2B5; D014316:Tritium; C061950:GYKI 52466; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D001569:Benzodiazepines; D001224:Aspartic Acid; D018698:Glutamic Acid; D013779:Tetrodotoxin; C020889:dihydrokainic acid; D005346:Fibroblast Growth Factors; D007608:Kainic Acid; D001640:Bicuculline