AutoriMarchetti, Carla; Baranowska-Bosiacka, Irena; Gavazzo, Paola
AbstractCopper (Cu) is an essential metal present in the human brain and released from synaptic vesicles following neuronal depolarization. Cu is known to reduce the NMDA receptor (NR) current with IC50 approximate to 20 mu M. We have studied the effect of Cu on the NR current in cultured neonatal rat cerebellum granule cells (CGC) and in transiently transfected HEK293 cells (HEK), expressing either GluN1/GLUN2A or GluN1/GluN2B receptors. In CGCs, Cu causes a potentiation of the NR current at concentrations <30 mu M (EC50=4.6 mu M) and a block at higher concentrations (IC50=24 mu M). In Fura2 loaded CG.Cs, Cu (<= 30 mu M) caused an increase of NMDA-driven calcium influx. This facilitating effect was prevented by pre-treatment with the reducing agent DTT. Cu also caused an increase of the NR current in GluN1/GluN2A receptors (EC50=2 mu M) and a block at higher concentrations (IC50=26 mu M). Both facilitation and inhibition were independent of voltage. The effect of Cu was quantitatively similar in GluN1/G1uN2B receptors, which were potentiated by 10 mu M and inhibited by 100 mu M Cu. Potentiation was absent in mutants deleted of their entire amino terminal domain (ATD) of the protein, suggesting an involvement of this region in the interaction. These results indicate that Cu can facilitate the NR current at lower concentrations than those required for blocking it; this effect can have consequences on the activity of the metal at synaptic and extrasynaptic sites. (C) 2013 Elsevier B.V. All rights reserved.
RivistaBrain Research
Impact factor0
Pagina inizio20
Pagina fine31
Linee di Ricerca IBFMD.P01.009.001