Document Detail

Sulfate- and size-dependent polysaccharide modulation of AMPA receptor properties.
MedLine Citation:
PMID:  14743454     Owner:  NLM     Status:  MEDLINE    
Previous work found evidence that alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-type glutamate receptors interact with and are functionally regulated by the glycosaminoglycan heparin. The present study tested whether dextran species affect ligand binding, channel kinetics, and calcium permeability of AMPA receptors. Dextran sulfate of 500 kDa markedly reduced high affinity [3H]AMPA binding in solubilized hippocampal membranes. In isolated receptors reconstituted in a lipid bilayer, the same dextran sulfate prolonged the lifetime of open states exhibited by AMPA-induced channel fluctuations. The large polysaccharide further changed the single channel kinetics by increasing the open channel probability five- to sixfold. Such modulation of channel activity corresponded with enhanced levels of calcium influx as shown in hippocampal neurons loaded with Fluo3AM dye. With an exposure time of <1 min, AMPA produced a dose-dependent increase in intracellular calcium that was blocked by 6-cyano-7-nitroquinoxaline-2,3-dione disodium (CNQX). Dextran sulfate, at the same concentration range that modified ligand binding (EC50 of 5-10 nM), enhanced the AMPA-induced calcium influx by as much as 60%. The enhanced influx was blocked by CNQX, although unchanged by the N-methyl-D-aspartate (NMDA) receptor antagonist AP5. Confocal microscopy showed that the increase in calcium occurred in neuronal cell bodies and their processes. Interestingly, smaller 5-8-kDa dextran sulfate and a non-sulfated dextran of 500 kDa had little or no effect on the binding, channel, and calcium permeability properties. Together, these findings suggest that synaptic polysaccharide species modulate hippocampal AMPA receptors in a sulfate- and size-dependent manner.
Linda M Chicoine; Vishnu Suppiramaniam; Thirumalini Vaithianathan; Gerald Gianutsos; Ben A Bahr
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of neuroscience research     Volume:  75     ISSN:  0360-4012     ISO Abbreviation:  J. Neurosci. Res.     Publication Date:  2004 Feb 
Date Detail:
Created Date:  2004-01-26     Completed Date:  2004-03-12     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7600111     Medline TA:  J Neurosci Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  408-16     Citation Subset:  IM    
Copyright Information:
Copyright 2003 Wiley-Liss, Inc.
Department of Pharmaceutical Sciences and the Neurosciences Program, University of Connecticut, Storrs, USA.
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MeSH Terms
6-Cyano-7-nitroquinoxaline-2,3-dione / pharmacology
Calcium / metabolism
Cells, Cultured
Dextran Sulfate / chemistry,  pharmacology*
Excitatory Amino Acid Antagonists / pharmacology
Hippocampus / drug effects*,  physiology
Microscopy, Confocal
Neurons / drug effects,  physiology
Rats, Sprague-Dawley
Receptors, AMPA / drug effects*,  physiology*
Grant Support
Reg. No./Substance:
0/Excitatory Amino Acid Antagonists; 0/Receptors, AMPA; 115066-14-3/6-Cyano-7-nitroquinoxaline-2,3-dione; 7440-70-2/Calcium; 9042-14-2/Dextran Sulfate

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