Src potentiation of NMDA receptors in hippocampal and spinal neurons is not mediated by reducing zinc inhibition.
The protein-tyrosine kinase Src is known to potentiate the function of NMDA receptors, which is necessary for the induction of long-term potentiation in the hippocampus. With recombinant receptors composed of NR1-1a/NR2A or NR1-1a/2B subunits, Src reduces voltage-independent inhibition by the divalent cation Zn2+. Thereby the function of recombinant NMDA receptors is potentiated by Src only when the Zn2+ level is sufficient to cause tonic inhibition. Here we investigated whether the Src-induced potentiation of NMDA receptor function in neurons is caused by reducing voltage-independent Zn2+ inhibition. Whereas chelating extracellular Zn2+ blocked the Src-induced potentiation of NR1-1a/2A receptors, we found that Zn2+ chelation did not affect the potentiation of NMDA receptor (NMDAR) currents by Src applied into hippocampal CA1 or CA3 neurons. Moreover, Src did not alter the Zn2+ concentration-inhibition relationship for NMDAR currents in CA1 or CA3 neurons. Also, chelating extracellular Zn2+ did not prevent the upregulation of NMDA single-channel activity by endogenous Src in membrane patches from spinal dorsal horn neurons. Taking these results together we conclude that Src-induced potentiation of NMDAR currents is not mediated by reducing Zn2+ inhibition in hippocampal and dorsal horn neurons.
Xiong
Z G
ZG
Department of Physiology, Programme in Brain and Behavior, Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8.
Pelkey
K A
KA
Lu
W Y
WY
Lu
Y M
YM
Roder
J C
JC
MacDonald
J F
JF
Salter
M W
MW
D000818:Animals; D004594:Electrophysiology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D015032:Zinc / Q000494:pharmacology*; D019061:src-Family Kinases / Q000502:physiology*
D016194:Receptors, N-Methyl-D-Aspartate; D019061:src-Family Kinases; D015032:Zinc