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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
10
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pubmed:dateCreated |
1997-6-2
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pubmed:abstractText |
Ca2+/calmodulin dependent protein kinase (CaMKII) and protein phosphatase 2B (calcineurin) are key enzymes in the regulation of synaptic strength, controlling the phosphorylation status of pre- and postsynaptic target proteins. Here, we show that the inactivation gating of the Shaker-related fast-inactivating KV channel, Kv1.4 is controlled by CaMKII and the calcineurin/inhibitor-1 protein phosphatase cascade. CaMKII phosphorylation of an amino-terminal residue of KV1.4 leads to slowing of inactivation gating and accelerated recovery from N-type inactivated states. In contrast, dephosphorylation of this residue induces a fast inactivating mode of KV1.4 with time constants of inactivation 5 to 10 times faster compared with the CaMKII-phosphorylated form. Dephosphorylated KV1.4 channels also display slowed and partial recovery from inactivation with increased trapping of KV1.4 channels in long-absorbing C-type inactivated states. In consequence, dephosphorylated KV1.4 displays a markedly increased tendency to undergo cumulative inactivation during repetitive stimulation. The balance between phosphorylated and dephosphorylated KV1.4 channels is regulated by changes in intracellular Ca2+ concentration rendering KV1.4 inactivation gating Ca2+-sensitive. The reciprocal CaMKII and calcineurin regulation of cumulative inactivation of presynaptic KV1.4 may provide a novel mechanism to regulate the critical frequency for presynaptic spike broadening and induction of synaptic plasticity.
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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 |
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0270-6474
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
17
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3379-91
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:9133364-Animals,
pubmed-meshheading:9133364-Calcineurin,
pubmed-meshheading:9133364-Calcium,
pubmed-meshheading:9133364-Calcium-Calmodulin-Dependent Protein Kinase Type 2,
pubmed-meshheading:9133364-Calcium-Calmodulin-Dependent Protein Kinases,
pubmed-meshheading:9133364-Calmodulin-Binding Proteins,
pubmed-meshheading:9133364-Cell Line,
pubmed-meshheading:9133364-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:9133364-Humans,
pubmed-meshheading:9133364-Ion Channel Gating,
pubmed-meshheading:9133364-Kidney,
pubmed-meshheading:9133364-Kinetics,
pubmed-meshheading:9133364-Mammals,
pubmed-meshheading:9133364-Mutagenesis, Site-Directed,
pubmed-meshheading:9133364-Patch-Clamp Techniques,
pubmed-meshheading:9133364-Phosphoprotein Phosphatases,
pubmed-meshheading:9133364-Phosphorylation,
pubmed-meshheading:9133364-Potassium,
pubmed-meshheading:9133364-Potassium Channels,
pubmed-meshheading:9133364-Shaker Superfamily of Potassium Channels,
pubmed-meshheading:9133364-Transfection
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pubmed:year |
1997
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pubmed:articleTitle |
Frequency-dependent inactivation of mammalian A-type K+ channel KV1.4 regulated by Ca2+/calmodulin-dependent protein kinase.
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pubmed:affiliation |
Zentrum für Molekulare Neurobiologie, Martinistrasse 52, D-20246 Hamburg, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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