Abstract
The activation-inactivation properties of membrane currents induced by the rapid application of glutamate or kainate were studied in cultured hippocampal neurons and in HEK cells transfected with a cDNA encoding the GluR6 subunit. The onset of desensitization was rapid and similar in native and recombinant channels (~80 s-1 of onset rate constant). Recovery from desensitization was slow and agonist-dependent in neurons, proceeding slightly faster in GluR6 receptors. Half-maximal activation (EC50) of native channels was obtained at a glutamate concentration of 330 μM, while the half-maximal steady state desensitization (IC(1/2)) was attained at 2.8 μM. These values differed from those obtained in recombinant receptors (EC50=762 μM and IC(1/2)=0.44 μM). A small window under the crossing point of activation and inactivation curves was observed, indicating that, for some concentrations of either agonist, steady state channel activity could exist. In native receptors, this window presented maximum values at approximately 100 μM for glutamate, which predicted well the potency of glutamate to reduce the GABAergic drive in hippocampal slices. These data indicate that for neuronal kainate receptors, the concentrations for half activation and half inactivation differ by two orders of magnitude such that the maximum response to a maintained concentration of glutamate is small, and the steady state dose response curve is skewed and bell shaped. Copyright (C) 1998 Elsevier Science Ltd.
Original language | English |
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Pages (from-to) | 1249-1259 |
Number of pages | 11 |
Journal | Neuropharmacology |
Volume | 37 |
Issue number | 10-11 |
DOIs | |
Publication status | Published - Oct 1 1998 |
Externally published | Yes |
Bibliographical note
Funding Information:We thank Dr P.H. Seeburg, from the Center for Molecular Biology, University of Heidelberg, for the CMV expression plasmid encoding GluR6 (VCQ), T.E. Hughes, from Yale University School of Medicine, for the plasmid encoding Green Fluorescent Protein (GFP), Elli Lilly and Co. (Indianapolis, IN) for the generous gift of GYKI 53655, Dr M.A. Nieto for critical reading of the manuscript, Dr M. Sefton for proof reading and D. Guinea for technical assistance. This work was supported in part by grants to JL from the DGICYT (UE96/007 and PM96/0008), FIS (95/0869), the Community of Madrid (AE00362/95) and the Biotech Programme of the European Community (BIO2-CT930243). AVP held a fellowship from Glaxo S.A. AV was supported by the Ministry of Education under the `Programa de Reincorporación', and AR-M by a FPI fellowship.
ASJC Scopus Subject Areas
- Pharmacology
- Cellular and Molecular Neuroscience
PubMed: MeSH publication types
- Comparative Study
- Journal Article
- Research Support, Non-U.S. Gov't