The receptor subunits generating NMDA receptor mediated currents in oligodendrocytes.
NMDA receptors have been shown to contribute to glutamate-evoked currents in oligodendrocytes. Activation of these receptors damages myelin in ischaemia, in part because they are more weakly blocked by Mg(2+) than are most neuronal NMDA receptors. This weak Mg(2+) block was suggested to reflect an unusual subunit composition including the NR2C and NR3A subunits. Here we expressed NR1/NR2C and triplet NR1/NR2C/NR3A recombinant receptors in HEK cells and compared their currents with those of NMDA-evoked currents in rat cerebellar oligodendrocytes. NR1/NR2C/3A receptors were less blocked by 2 mM Mg(2+) than were NR1/NR2C receptors (the remaining current was 30% and 18%, respectively, of that seen without added Mg(2+)) and showed less channel noise, suggesting a smaller single channel conductance. NMDA-evoked currents in oligodendrocytes showed a Mg(2+) block (to 32%) similar to that observed for NR1/NR2C/NR3A and significantly different from that for NR1/NR2C receptors. Co-immunoprecipitation revealed interactions between NR1, NR2C and NR3A subunits in a purified myelin preparation from rat brain. These data are consistent with NMDA-evoked currents in oligodendrocytes reflecting the activation of receptors containing NR1, NR2C and NR3A subunits.
Burzomato
Valeria
V
Department of Neuroscience, Physiology and Pharmacology, University College London, Gower Street, London WC1E 6BT, UK.
Frugier
Guillaume
G
Pérez-Otaño
Isabel
I
Kittler
Josef T
JT
Attwell
David
D
D000818:Animals; D002531:Cerebellum / Q000166:cytology; D055724:Electrophysiological Phenomena; D005071:Evoked Potentials / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D057809:HEK293 Cells; D006801:Humans; D008274:Magnesium / Q000494:pharmacology; D009836:Oligodendroglia / Q000502:physiology*; D020033:Protein Isoforms; D021122:Protein Subunits; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*
D020033:Protein Isoforms; D021122:Protein Subunits; D016194:Receptors, N-Methyl-D-Aspartate; D008274:Magnesium