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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2001-8-8
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pubmed:abstractText |
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA-R)-mediated neurotoxicity was studied in relation to subunit expression and the presence of Ca(2+)-permeable receptor channels. AMPA-mediated toxicity had two components: 1) a direct AMPA-R-mediated component, which was not due to Ca(2+) influx through voltage-gated Ca(2+) channels, reversal of the Na(+)/Ca(2+) exchanger or release of calcium from dantrolene-sensitive intracellular Ca(2+) stores, and 2) a minor, indirect component involving activation of NMDA receptor channels, because of glutamate release and removal of the Mg(2+) block of the NMDA receptor on AMPA-R stimulation. The involvement of Ca(2+) influx through AMPA-R was also examined. The number of neurons possessing Ca(2+)-permeable AMPA-R increased during culture development, concurrently with an increasing susceptibility for AMPA-induced toxicity during development. GluR2(R) levels also increased during development, and channel blockers of Ca(2+)-permeable AMPA-R lacking the GluR2(R) subunit (spermine and philanthotoxin) failed to prevent neurotoxicity or increases in [Ca(2+)](i). Thus, the direct AMPA-R-mediated toxicity may be explained by initiation of cell death by Ca(2+) fluxing through AMPA-R containing GluR2(R). The components of direct AMPA-R-mediated toxicity are proposed to be 1) toxicity mediated by GluR2(R)-lacking AMPA-R and 2) toxicity mediated by low-Ca(2+)-permeability AMPA-R containing GluR2(R).
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Benzothiadiazines,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channel Blockers,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Dizocilpine Maleate,
http://linkedlifedata.com/resource/pubmed/chemical/Excitatory Amino Acid Agonists,
http://linkedlifedata.com/resource/pubmed/chemical/Excitatory Amino Acid Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Flunarizine,
http://linkedlifedata.com/resource/pubmed/chemical/Lanthanum,
http://linkedlifedata.com/resource/pubmed/chemical/Macromolecular Substances,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Neuroprotective Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Nifedipine,
http://linkedlifedata.com/resource/pubmed/chemical/Polyamines,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Subunits,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, AMPA,
http://linkedlifedata.com/resource/pubmed/chemical/Sodium,
http://linkedlifedata.com/resource/pubmed/chemical/Sodium Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Sodium-Calcium Exchanger,
http://linkedlifedata.com/resource/pubmed/chemical/Spermine,
http://linkedlifedata.com/resource/pubmed/chemical/Tetrodotoxin,
http://linkedlifedata.com/resource/pubmed/chemical/alpha-Amino-3-hydroxy-5-methyl-4-iso...,
http://linkedlifedata.com/resource/pubmed/chemical/cyclothiazide,
http://linkedlifedata.com/resource/pubmed/chemical/delta-philanthotoxin,
http://linkedlifedata.com/resource/pubmed/chemical/glutamate receptor ionotropic...,
http://linkedlifedata.com/resource/pubmed/chemical/omega-Conotoxins,
http://linkedlifedata.com/resource/pubmed/chemical/omega-conotoxin-MVIIC
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0360-4012
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pubmed:author |
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pubmed:copyrightInfo |
Copyright 2001 Wiley-Liss, Inc.
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
65
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
267-77
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:11494361-Animals,
pubmed-meshheading:11494361-Apoptosis,
pubmed-meshheading:11494361-Benzothiadiazines,
pubmed-meshheading:11494361-Calcium,
pubmed-meshheading:11494361-Calcium Channel Blockers,
pubmed-meshheading:11494361-Calcium Channels,
pubmed-meshheading:11494361-Calcium Signaling,
pubmed-meshheading:11494361-Cells, Cultured,
pubmed-meshheading:11494361-Cerebral Cortex,
pubmed-meshheading:11494361-Dizocilpine Maleate,
pubmed-meshheading:11494361-Excitatory Amino Acid Agonists,
pubmed-meshheading:11494361-Excitatory Amino Acid Antagonists,
pubmed-meshheading:11494361-Flunarizine,
pubmed-meshheading:11494361-Gene Expression Regulation, Developmental,
pubmed-meshheading:11494361-Ion Channel Gating,
pubmed-meshheading:11494361-Lanthanum,
pubmed-meshheading:11494361-Macromolecular Substances,
pubmed-meshheading:11494361-Mice,
pubmed-meshheading:11494361-Nerve Tissue Proteins,
pubmed-meshheading:11494361-Neurons,
pubmed-meshheading:11494361-Neuroprotective Agents,
pubmed-meshheading:11494361-Nifedipine,
pubmed-meshheading:11494361-Polyamines,
pubmed-meshheading:11494361-Protein Subunits,
pubmed-meshheading:11494361-Receptors, AMPA,
pubmed-meshheading:11494361-Sodium,
pubmed-meshheading:11494361-Sodium Channels,
pubmed-meshheading:11494361-Sodium-Calcium Exchanger,
pubmed-meshheading:11494361-Spermine,
pubmed-meshheading:11494361-Tetrodotoxin,
pubmed-meshheading:11494361-alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid,
pubmed-meshheading:11494361-omega-Conotoxins
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pubmed:year |
2001
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pubmed:articleTitle |
Role of GluR2 expression in AMPA-induced toxicity in cultured murine cerebral cortical neurons.
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pubmed:affiliation |
The Royal Danish School of Pharmacy, NeuroScience PharmaBiotech Research Center, Department of Pharmacology, 2 Universitetsparken, DK-2100 Copenhagen, Denmark.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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