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The Journal of Neuroscience, 1999, 19:RC37:1-6

RAPID COMMUNICATION
Src Potentiation of NMDA Receptors in Hippocampal and Spinal Neurons Is Not Mediated by Reducing Zinc Inhibition

Zhi-gang Xiong¹, Kenneth A. Pelkey^{1, 2}, Wei Yang Lu¹, You Ming Lu³, John C. Roder³, John F. MacDonald¹, and Michael W. Salter^{1, 2}

¹ Department of Physiology, ² Programme in Brain and Behavior, Hospital for Sick Children, and ³ Samuel Lunenfeld Research Institute, Mount Sinai Hospital, and Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario, Canada M5G 1X8

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.

Key words: NMDA; Src; Zinc; hippocampus; spinal dorsal horn; EDTA

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Copyright © 0000 Society for Neuroscience  0270-6474/0/$05.00/0

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