Document Detail


The Kv2.1 channels mediate neuronal apoptosis induced by excitotoxicity.
MedLine Citation:
PMID:  19077057     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Chronic loss of intracellular K(+) can induce neuronal apoptosis in pathological conditions. However, the mechanism by which the K(+) channels are regulated in this process remains largely unknown. Here, we report that the increased membrane expression of Kv2.1 proteins in cortical neurons deprived of serum, a condition known to induce K(+) loss, promotes neuronal apoptosis. The increase in I(K) current density and apoptosis in the neurons deprived of serum were inhibited by a dominant negative form of Kv2.1 and MK801, an antagonist to NMDA receptors. The membrane level of Kv2.1 and its interaction with SNAP25 were increased, whereas the Kv2.1 phosphorylation was inhibited in the neurons deprived of serum. Botulinum neurotoxin, an agent known to prevent formation of soluble N-ethylmaleimide-sensitive factor attachment protein receptor complex, suppressed the increase in I(K) current density. Together, these results suggest that NMDA receptor-dependent Kv2.1 membrane translocation is regulated by a soluble N-ethylmaleimide-sensitive factor attachment protein receptor-dependent vesicular trafficking mechanism and is responsible for neuronal cell death induced by chronic loss of K(+).
Authors:
Hailan Yao; Kechun Zhou; Dong Yan; Mingtao Li; Yizheng Wang
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-12-10
Journal Detail:
Title:  Journal of neurochemistry     Volume:  108     ISSN:  1471-4159     ISO Abbreviation:  J. Neurochem.     Publication Date:  2009 Feb 
Date Detail:
Created Date:  2009-02-06     Completed Date:  2009-04-20     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985190R     Medline TA:  J Neurochem     Country:  England    
Other Details:
Languages:  eng     Pagination:  909-19     Citation Subset:  IM    
Affiliation:
The Graduate School, Chinese Academy of Science, Shanghai, China.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / drug effects,  physiology*
Botulinum Toxins / pharmacology
Cell Membrane / genetics,  metabolism
Cells, Cultured
Cerebral Cortex / cytology,  drug effects,  metabolism*
Culture Media, Serum-Free / pharmacology
Excitatory Amino Acid Antagonists / pharmacology
N-Ethylmaleimide-Sensitive Proteins / metabolism
Neuromuscular Agents / pharmacology
Neurons / drug effects,  metabolism*
Neurotoxins / metabolism*,  pharmacology
Patch-Clamp Techniques
Potassium / metabolism
Potassium Deficiency / metabolism*,  physiopathology
Protein Transport / drug effects,  physiology
Rats
Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors,  metabolism
Shab Potassium Channels / drug effects,  genetics,  metabolism*
Synaptosomal-Associated Protein 25 / metabolism
Transport Vesicles / metabolism
Chemical
Reg. No./Substance:
0/Botulinum Toxins; 0/Culture Media, Serum-Free; 0/Excitatory Amino Acid Antagonists; 0/Kcnb1 protein, rat; 0/Neuromuscular Agents; 0/Neurotoxins; 0/Nsf protein, rat; 0/Receptors, N-Methyl-D-Aspartate; 0/Shab Potassium Channels; 0/Snap25 protein, rat; 0/Synaptosomal-Associated Protein 25; 7440-09-7/Potassium; EC 3.6.4.6/N-Ethylmaleimide-Sensitive Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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