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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2008-12-19
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pubmed:abstractText |
The lipid diacylglycerol (DAG) analogue 1-oleoyl-2-acetyl-sn-glycerol (OAG) was used to verify the existence of DAG-sensitive channels in cortical neurons dissociated from E13 mouse embryos. Calcium imaging experiments showed that OAG increased the cytosolic concentration of Ca(2+) ([Ca(2+)]i) in nearly 35% of the KCl-responsive cells. These Ca(2+) responses disappeared in a Ca(2+)-free medium supplemented with EGTA. Mn(2+) quench experiments showed that OAG activated Ca(2+)-conducting channels that were also permeant to Ba(2+). The OAG-induced Ca(2+) responses were unaffected by nifedipine or omega-conotoxin GVIA (Sigma-Aldrich, Saint-Quentin Fallavier, France) but blocked by 1-[beta-(3-(4-Methoxyphenyl)propoxy)-4-methoxyphenethyl]-1H-imidazole hydrochloride (SKF)-96365 and Gd(3+). Replacing Na(+) ions with N-methyl-D-glucamine diminished the amplitude of the OAG-induced Ca(2+) responses showing that the Ca(2+) entry was mediated via Na(+)-dependent and Na(+)-independent mechanisms. Experiments carried out with the fluorescent Na(+) indicator CoroNa Green showed that OAG elevated [Na(+)]i. Like OAG, the DAG lipase inhibitor RHC80267 increased [Ca(2+)]i but not the protein kinase C activator phorbol 12-myristate 13-acetate. Moreover, the OAG-induced Ca(2+) responses were not regulated by protein kinase C activation or inhibition but they were augmented by flufenamic acid which increases currents through C-type transient receptor potential protein family (TRPC) 6 channels. In addition, application of hyperforin, a specific activator of TRPC6 channels, elevated [Ca(2+)]i. Whole-cell patch-clamp recordings showed that hyperforin activated non-selective cation channels. They were blocked by SKF-96365 but potentiated by flufenamic acid. Altogether, our data show the presence of hyperforin- and OAG-sensitive Ca(2+)-permeable channels displaying TRPC6-like properties. This is the first report revealing the existence of second messenger-operated channels in cortical neurons.
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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/1,6-bis(cyclohexyloximinocarbonyl)he...,
http://linkedlifedata.com/resource/pubmed/chemical/1-oleoyl-2-acetoyl-sn-glycerol,
http://linkedlifedata.com/resource/pubmed/chemical/Aniline Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Bicyclo Compounds,
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/Cyclohexanones,
http://linkedlifedata.com/resource/pubmed/chemical/Diglycerides,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Fluo 4,
http://linkedlifedata.com/resource/pubmed/chemical/Fura-2,
http://linkedlifedata.com/resource/pubmed/chemical/Phloroglucinol,
http://linkedlifedata.com/resource/pubmed/chemical/Potassium Chloride,
http://linkedlifedata.com/resource/pubmed/chemical/Sodium,
http://linkedlifedata.com/resource/pubmed/chemical/TRPC Cation Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Terpenes,
http://linkedlifedata.com/resource/pubmed/chemical/Xanthenes,
http://linkedlifedata.com/resource/pubmed/chemical/hyperforin
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1471-4159
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
108
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
126-38
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pubmed:meshHeading |
pubmed-meshheading:19094061-Aniline Compounds,
pubmed-meshheading:19094061-Animals,
pubmed-meshheading:19094061-Bicyclo Compounds,
pubmed-meshheading:19094061-Calcium,
pubmed-meshheading:19094061-Calcium Channel Blockers,
pubmed-meshheading:19094061-Calcium Channels,
pubmed-meshheading:19094061-Cells, Cultured,
pubmed-meshheading:19094061-Cerebral Cortex,
pubmed-meshheading:19094061-Cyclohexanones,
pubmed-meshheading:19094061-Diglycerides,
pubmed-meshheading:19094061-Embryo, Mammalian,
pubmed-meshheading:19094061-Enzyme Inhibitors,
pubmed-meshheading:19094061-Fura-2,
pubmed-meshheading:19094061-Membrane Potentials,
pubmed-meshheading:19094061-Mice,
pubmed-meshheading:19094061-Mice, Inbred C57BL,
pubmed-meshheading:19094061-Neurons,
pubmed-meshheading:19094061-Patch-Clamp Techniques,
pubmed-meshheading:19094061-Phloroglucinol,
pubmed-meshheading:19094061-Potassium Chloride,
pubmed-meshheading:19094061-Second Messenger Systems,
pubmed-meshheading:19094061-Sodium,
pubmed-meshheading:19094061-TRPC Cation Channels,
pubmed-meshheading:19094061-Terpenes,
pubmed-meshheading:19094061-Xanthenes
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pubmed:year |
2009
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pubmed:articleTitle |
Diacylglycerol analogues activate second messenger-operated calcium channels exhibiting TRPC-like properties in cortical neurons.
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pubmed:affiliation |
CNRS UMR 5249, Grenoble, France.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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