QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Xiong, Z.-g. Articles by Salter, M. W. Search for Related Content PubMed PubMed Citation Articles by Xiong, Z.-g. Articles by Salter, M. W.

 Previous Article  |  Next Article 

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

---

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

This article has been cited by other articles:

				B. Murphy, M. Dunleavy, S. Shinoda, C. Schindler, R. Meller, C. Bellver-Estelles, S. Hatazaki, P. Dicker, A. Yamamoto, I. Koegel, et al. Bcl-w Protects Hippocampus during Experimental Status Epilepticus Am. J. Pathol., October 1, 2007; 171(4): 1258 - 1268. [Abstract] [Full Text] [PDF]

				X.-P. Chu, N. Close, J. A. Saugstad, and Z.-G. Xiong ASIC1a-specific modulation of acid-sensing ion channels in mouse cortical neurons by redox reagents. J. Neurosci., May 17, 2006; 26(20): 5329 - 5339. [Abstract] [Full Text] [PDF]

				M. Sanchez-Alavez, I. V. Tabarean, M. M. Behrens, and T. Bartfai Ceramide mediates the rapid phase of febrile response to IL-1beta PNAS, February 21, 2006; 103(8): 2904 - 2908. [Abstract] [Full Text] [PDF]

				X.-P. Chu, J. A. Wemmie, W.-Z. Wang, X.-M. Zhu, J. A. Saugstad, M. P. Price, R. P. Simon, and Z.-G. Xiong Subunit-Dependent High-Affinity Zinc Inhibition of Acid-Sensing Ion Channels J. Neurosci., October 6, 2004; 24(40): 8678 - 8689. [Abstract] [Full Text] [PDF]

				G. K. Seabold, A. Burette, I. A. Lim, R. J. Weinberg, and J. W. Hell Interaction of the Tyrosine Kinase Pyk2 with the N-Methyl-D-aspartate Receptor Complex via the Src Homology 3 Domains of PSD-95 and SAP102 J. Biol. Chem., April 18, 2003; 278(17): 15040 - 15048. [Abstract] [Full Text] [PDF]

				P. Benquet, C. E. Gee, and U. Gerber Two Distinct Signaling Pathways Upregulate NMDA Receptor Responses via Two Distinct Metabotropic Glutamate Receptor Subtypes J. Neurosci., November 15, 2002; 22(22): 9679 - 9686. [Abstract] [Full Text] [PDF]

				W. Guo, S. Zou, Y. Guan, T. Ikeda, M. Tal, R. Dubner, and K. Ren Tyrosine Phosphorylation of the NR2B Subunit of the NMDA Receptor in the Spinal Cord during the Development and Maintenance of Inflammatory Hyperalgesia J. Neurosci., July 15, 2002; 22(14): 6208 - 6217. [Abstract] [Full Text] [PDF]

				V. Heidinger, P. Manzerra, X. Q. Wang, U. Strasser, S.-P. Yu, D. W. Choi, and M. M. Behrens Metabotropic Glutamate Receptor 1-Induced Upregulation of NMDA Receptor Current: Mediation through the Pyk2/Src-Family Kinase Pathway in Cortical Neurons J. Neurosci., July 1, 2002; 22(13): 5452 - 5461. [Abstract] [Full Text] [PDF]

				X.-P. Chu, J. Miesch, M. Johnson, L. Root, X.-M. Zhu, D. Chen, R. P. Simon, and Z.-G. Xiong Proton-Gated Channels in PC12 Cells J Neurophysiol, May 1, 2002; 87(5): 2555 - 2561. [Abstract] [Full Text] [PDF]

				M. B. Kennedy and P. Manzerra Telling tails PNAS, October 23, 2001; 98(22): 12323 - 12324. [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help