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 Web of Science 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 Web of Science (22) Citing Articles via Google Scholar Google Scholar Articles by Iihara, K. Articles by Tymianski, M. Search for Related Content PubMed PubMed Citation Articles by Iihara, K. Articles by Tymianski, M.

 Previous Article  |  Next Article 

The Journal of Neuroscience, April 1, 2001, 21(7):2224-2239

The Influence of Glutamate Receptor 2 Expression on Excitotoxicity in GluR2 Null Mutant Mice

Koji Iihara¹, Daisy T. Joo², Jeffrey Henderson³, Rita Sattler¹, Franco A. Taverna³, Sandra Lourensen³, Beverley A. Orser², John C. Roder³, and Michael Tymianski¹

¹ Toronto Western Hospital, University of Toronto, Toronto, Ontario M5T-2S8, Canada, ² Department of Anesthesia, University of Toronto, Toronto, Ontario M5G-1X8, Canada, and ³ Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G-1X5, Canada

AMPA receptor (AMPAR)-mediated ionic currents that govern gene expression, synaptic strength, and plasticity also can trigger excitotoxicity. However, native AMPARs exhibit heterogeneous pharmacological, biochemical, and ionic permeability characteristics, which are governed partly by receptor subunit composition. Consequently, the mechanisms governing AMPAR-mediated excitotoxicity have been difficult to elucidate. The GluR2 subunit is of particular interest because it influences AMPAR pharmacology, Ca²⁺ permeability, and AMPAR interactions with intracellular proteins. In this paper we used mutant mice lacking the AMPAR subunit GluR2 to study AMPAR-mediated excitotoxicity in cultured cortical neurons and in hippocampal neurons in vivo. We examined the hypothesis that in these mice the level of GluR2 expression governs the vulnerability of neurons to excitotoxicity and further examined the ionic mechanisms that are involved. In cortical neuronal cultures AMPAR-mediated neurotoxicity paralleled the magnitude of kainate-evoked AMPAR-mediated currents, which were increased in neurons lacking GluR2. Ca²⁺ permeability, although elevated in GluR2-deficient neurons, did not correlate with excitotoxicity. However, toxicity was reduced by removal of extracellular Na⁺, the main charge carrier of AMPAR-mediated currents. In vivo, the vulnerability of CA1 hippocampal neurons to stereotactic kainate injections and of CA3 neurons to intraperitoneal kainate administration was independent of GluR2 level. Neurons lacking the GluR2 subunit did not demonstrate compensatory changes in the distribution, expression, or function of AMPARs or of Ca²⁺-buffering proteins. Thus GluR2 level may influence excitotoxicity by effects additional to those on Ca²⁺ permeability, such as effects on agonist potency, ionic currents, and synaptic reorganization.

Key words: AMPA receptors; kainate; excitotoxicity; GluR2 subunit; calcium permeability; cortical neurons

---

Copyright © 2001 Society for Neuroscience  0270-6474/01/2172224-16$05.00/0

This article has been cited by other articles:

				S. Ellefsen, G. K. Sandvik, H. K. Larsen, K.-O. Stenslokken, D. A. S. Hov, T. A. Kristensen, and G. E. Nilsson Expression of genes involved in excitatory neurotransmission in anoxic crucian carp (Carassius carassius) brain Physiol Genomics, September 17, 2008; 35(1): 5 - 17. [Abstract] [Full Text] [PDF]

				S. Zou, L. Li, L. Pei, B. Vukusic, H. H. M. Van Tol, F. J. S. Lee, Q. Wan, and F. Liu Protein-Protein Coupling/Uncoupling Enables Dopamine D2 Receptor Regulation of AMPA Receptor-Mediated Excitotoxicity J. Neurosci., April 27, 2005; 25(17): 4385 - 4395. [Abstract] [Full Text] [PDF]

				J. S. Erlichman, A. Cook, M. C. Schwab, T. W. Budd, and J. C. Leiter Heterogeneous patterns of pH regulation in glial cells in the dorsal and ventral medulla Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2004; 286(2): R289 - R302. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help