Source:http://linkedlifedata.com/resource/pubmed/id/10844014
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
12
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| pubmed:dateCreated |
2000-6-30
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| pubmed:abstractText |
The NMDA subtype of the glutamate-gated channel exhibits a high permeability to Ca(2+). The influx of Ca(2+) through NMDA channels is limited by a rapid and Ca(2+)/calmodulin (CaM)-dependent inactivation that results from a competitive displacement of cytoskeleton-binding proteins from the NR1 subunit of the receptor by Ca(2+)/CaM (Zhang et al., 1998; Krupp et al., 1999). The C terminal of this subunit can be phosphorylated by protein kinase C (PKC) (Tingley et al., 1993). The present study sought to investigate whether PKC regulates Ca(2+)-dependent inactivation of the NMDA channel in hippocampal neurons. Activation of endogenous PKC by 4beta-phorbol 12-myristate 13-acetate enhanced peak (I(p)) and depressed steady-state (I(ss)) NMDA-evoked currents, resulting in a reduction in the ratio of these currents (I(ss)/I(p)). We demonstrated previously that PKC activity enhances I(P) via a sequential activation of the focal adhesion kinase cell adhesion kinase beta/proline-rich tyrosine kinase 2 (CAKbeta/Pyk2) and the nonreceptor tyrosine kinase Src (Huang et al., 1999; Lu et al., 1999). Here, we report that the PKC-induced depression of I(ss) is unrelated to the PKC/CAKbeta/Src-signaling pathway but depends on the concentration of extracellular Ca(2+). Intracellular applications of CaM reduced I(ss)/I(p) and occluded the Ca(2+)-dependent effect of phorbol esters on I(ss.) Moreover, increasing the concentration of intracellular Ca(2+) buffer or intracellular application of the inhibitory CaM-binding peptide (KY9) greatly reduced the phorbol ester-induced depression of I(ss). Taken together, these results suggest that PKC enhances Ca(2+)/CaM-dependent inactivation of the NMDA channel, most likely because of a phosphorylation-dependent regulation of interactions between receptor subunits, CaM, and other postsynaptic density proteins.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Calmodulin,
http://linkedlifedata.com/resource/pubmed/chemical/Egtazic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Focal Adhesion Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Focal Adhesion Protein-Tyrosine...,
http://linkedlifedata.com/resource/pubmed/chemical/Glycine,
http://linkedlifedata.com/resource/pubmed/chemical/N-Methylaspartate,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Ptk2 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, N-Methyl-D-Aspartate,
http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jun
|
| pubmed:issn |
0270-6474
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
15
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| pubmed:volume |
20
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
4452-61
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:10844014-Animals,
pubmed-meshheading:10844014-Calcium,
pubmed-meshheading:10844014-Calmodulin,
pubmed-meshheading:10844014-Egtazic Acid,
pubmed-meshheading:10844014-Enzyme Activation,
pubmed-meshheading:10844014-Evoked Potentials,
pubmed-meshheading:10844014-Focal Adhesion Kinase 1,
pubmed-meshheading:10844014-Focal Adhesion Protein-Tyrosine Kinases,
pubmed-meshheading:10844014-Glycine,
pubmed-meshheading:10844014-Hippocampus,
pubmed-meshheading:10844014-Kinetics,
pubmed-meshheading:10844014-N-Methylaspartate,
pubmed-meshheading:10844014-Protein Kinase C,
pubmed-meshheading:10844014-Protein-Tyrosine Kinases,
pubmed-meshheading:10844014-Pyramidal Cells,
pubmed-meshheading:10844014-Rats,
pubmed-meshheading:10844014-Rats, Wistar,
pubmed-meshheading:10844014-Receptors, N-Methyl-D-Aspartate,
pubmed-meshheading:10844014-Tetradecanoylphorbol Acetate
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| pubmed:year |
2000
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| pubmed:articleTitle |
In CA1 pyramidal neurons of the hippocampus protein kinase C regulates calcium-dependent inactivation of NMDA receptors.
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| pubmed:affiliation |
Department of Physiology, University of Toronto, Toronto, Ontario M5S 1A8 Canada. w.lu@utoronto.ca
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| pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, Non-U.S. Gov't
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