HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 564/2/397    most recent jphysiol.2004.082131v1 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 Cavelier, P. Articles by Attwell, D. Search for Related Content PubMed PubMed Citation Articles by Cavelier, P. Articles by Attwell, D.

¹ Department of Physiology, University College London, Gower Street, London, WC1E 6BT, UK

Tonic release of glutamate into the extracellular space of the hippocampus and striatum is non-vesicular, and has been attributed largely to a cystine–glutamate exchanger which is blockable by the glutamate analogue (S)-4-carboxyphenylglycine (CPG). Tonic glutamate release may be functionally important: modulation of this release in the striatum has been suggested to underlie relapse in the use of cocaine. We monitored tonic glutamate release in area CA1 of hippocampal slices by measuring the glutamate receptor-mediated current evoked in pyramidal cells on block of Na⁺-dependent glutamate uptake with DL-threo-ß-benzyloxyaspartate (TBOA). Superfused cystine increased tonic glutamate release, and this increase was blocked by CPG, but CPG did not affect tonic glutamate release in the absence of superfused cystine. Tonic glutamate release was not affected by blocking gap junctional hemichannels with 18-glycyrrhetinic acid, blocking ATP receptors with pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), blocking Ca²⁺-dependent exocytosis from neurones with Cd²⁺ or bafilomycin, blocking Ca²⁺-dependent release from glia with indomethacin, or blocking anion channels with 5-nitro-2-(3-phenylpropyl amino) benzoic acid (NPPB) or tamoxifen. However tonic glutamate release was reduced by 4,4'-diisothiocyanostilbene-2,2'-disulphonic acid (DIDS), and was potentiated by inhibiting astrocytic conversion of glutamate to glutamine with methionine sulfoximine. These data suggest that although cystine–glutamate exchange is present in the hippocampus it does not generate significant tonic release of glutamate when the extracellular [cystine] is at a physiological level, and that tonic glutamate release is at least partly from astrocytes and is mediated by a DIDS-sensitive mechanism. Theoretical calculations suggest that a significant fraction of tonic glutamate release in hippocampal slices could occur via diffusion of glutamate across lipid membranes.

(Received 23 December 2004; accepted after revision 28 January 2005; first published online 3 February 2005)
Corresponding author D. Attwell: Department of Physiology, University College London, Gower Street, London WC1E 6BT, UK. Email: d.attwell{at}ucl.ac.uk

This article has been cited by other articles:

				P. J. Mulholland, E. P. Carpenter-Hyland, M. C. Hearing, H. C. Becker, J. J. Woodward, and L. J. Chandler Glutamate Transporters Regulate Extrasynaptic NMDA Receptor Modulation of Kv2.1 Potassium Channels J. Neurosci., August 27, 2008; 28(35): 8801 - 8809. [Abstract] [Full Text] [PDF]

				H. Misonou, S. M. Thompson, and X. Cai Dynamic Regulation of the Kv2.1 Voltage-Gated Potassium Channel during Brain Ischemia through Neuroglial Interaction J. Neurosci., August 20, 2008; 28(34): 8529 - 8538. [Abstract] [Full Text] [PDF]

				J. Petravicz, T. A. Fiacco, and K. D. McCarthy Loss of IP3 Receptor-Dependent Ca2+ Increases in Hippocampal Astrocytes Does Not Affect Baseline CA1 Pyramidal Neuron Synaptic Activity J. Neurosci., May 7, 2008; 28(19): 4967 - 4973. [Abstract] [Full Text] [PDF]

				D. J. Brasier and D. E. Feldman Synapse-Specific Expression of Functional Presynaptic NMDA Receptors in Rat Somatosensory Cortex J. Neurosci., February 27, 2008; 28(9): 2199 - 2211. [Abstract] [Full Text] [PDF]

				M. A. Herman and C. E. Jahr Extracellular Glutamate Concentration in Hippocampal Slice J. Neurosci., September 5, 2007; 27(36): 9736 - 9741. [Abstract] [Full Text] [PDF]

				J. Xu, H. Peng, N. Kang, Z. Zhao, J. H-C. Lin, P. K. Stanton, and J. Kang Glutamate-induced Exocytosis of Glutamate from Astrocytes J. Biol. Chem., August 17, 2007; 282(33): 24185 - 24197. [Abstract] [Full Text] [PDF]

				K. L. Meur, M. Galante, M. C. Angulo, and E. Audinat Tonic activation of NMDA receptors by ambient glutamate of non-synaptic origin in the rat hippocampus J. Physiol., April 15, 2007; 580(2): 373 - 383. [Abstract] [Full Text] [PDF]

				S. G. Owe, P. Marcaggi, and D. Attwell The ionic stoichiometry of the GLAST glutamate transporter in salamander retinal glia J. Physiol., December 1, 2006; 577(2): 591 - 599. [Abstract] [Full Text] [PDF]