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

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, September 24, 2003, 23(25):8641-8648

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 (10) Citing Articles via Google Scholar Google Scholar Articles by Paternain, A. V. Articles by Lerma, J. Search for Related Content PubMed PubMed Citation Articles by Paternain, A. V. Articles by Lerma, J.

 Previous Article  |  Next Article 

Cellular/Molecular
A Role for Extracellular Na⁺ in the Channel Gating of Native and Recombinant Kainate Receptors

Ana V. Paternain,¹ Adir Cohen,² Yael Stern-Bach,² and Juan Lerma¹

¹Instituto Cajal, Consejo Superior de Investigaciones Científicas, 28002 Madrid, Spain, and ²The Institute of Basic Dental Sciences, The Hebrew University-Hadassah School of Dental Medicine, 91120 Jerusalem, Israel

Ionotropic glutamate receptors of the kainate and AMPA subtypes share a number of structural features, both topographical and in terms of stoichiometry. In addition, AMPA and kainate receptors share similar pharmacological and biophysical properties in that they are activated by common agonists and display rapid activation and desensitization characteristics. However, we show here that in contrast to AMPA receptor-mediated responses (native or recombinant GluR3 receptor), the response of native and recombinant (GluR6) kainate receptors to glutamate was drastically reduced in the absence of extracellular Na⁺ (i.e., when replaced by Cs⁺). Removal of Na⁺ increases the rate of desensitization, indicating that external Na⁺ modulates channel gating. Whereas the size of the substituting cation is important in mimicking the action of Na⁺ (Li⁺>K⁺>Cs⁺), modulation was voltage independent. These results indicate the existence of different gating mechanisms for AMPA and kainate receptors. By using chimeric AMPA-kainate receptors derived from GluR3 and GluR6, we have identified a key residue in the S2 segment of GluR6 (M770) that is largely responsible for the sensitivity of the receptor to external Na⁺. Thus, these results show the existence of a specific kainate receptor gating mechanism that requires external Na⁺ to be operative.

Key words: kainate; glutamate; GluR6; KA2; GluR3; AMPA; channel gating; structure-function; allosteric modulation; receptors; chimeras

---

Received Feb 21, 2003; revised July 9, 2003; accepted July 10, 2003.

This article has been cited by other articles:

				A. Barberis, S. Sachidhanandam, and C. Mulle GluR6/KA2 Kainate Receptors Mediate Slow-Deactivating Currents J. Neurosci., June 18, 2008; 28(25): 6402 - 6406. [Abstract] [Full Text] [PDF]

				A. Y. C. Wong, D. M. MacLean, and D. Bowie Na+/Cl- Dipole Couples Agonist Binding to Kainate Receptor Activation J. Neurosci., June 20, 2007; 27(25): 6800 - 6809. [Abstract] [Full Text] [PDF]

				A. Y. C. Wong, A.-M. L. Fay, and D. Bowie External Ions Are Coactivators of Kainate Receptors J. Neurosci., May 24, 2006; 26(21): 5750 - 5755. [Abstract] [Full Text] [PDF]

				M. H. Nanao, T. Green, Y. Stern-Bach, S. F. Heinemann, and S. Choe Structure of the kainate receptor subunit GluR6 agonist-binding domain complexed with domoic acid PNAS, February 1, 2005; 102(5): 1708 - 1713. [Abstract] [Full Text] [PDF]

				J. K. Christensen, A. V. Paternain, S. Selak, P. K. Ahring, and J. Lerma A Mosaic of Functional Kainate Receptors in Hippocampal Interneurons J. Neurosci., October 13, 2004; 24(41): 8986 - 8993. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help