Source:http://linkedlifedata.com/resource/pubmed/id/17093127
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
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| pubmed:dateCreated |
2007-1-17
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| pubmed:abstractText |
Down syndrome (DS) is the most common nonheritable cause of mental retardation. DS is the result of the presence of an extra chromosome 21 and its phenotype may be a consequence of overexpressed genes from that chromosome. One such gene is Kcnj6/Girk2, which encodes the G-protein-coupled inward rectifying potassium channel subunit 2 (GIRK2). We have recently shown that the DS mouse model, Ts65Dn, overexpresses GIRK2 throughout the brain and in particular the hippocampus. Here we report that this overexpression leads to a significant increase ( approximately 2-fold) in GABA(B)-mediated GIRK current in primary cultured hippocampal neurons. The dose response curves for peak and steady-state GIRK current density is significantly shifted left toward lower concentrations of baclofen in Ts65Dn neurons compared with diploid controls, consistent with increased functional expression of GIRK channels. Stationary fluctuation analysis of baclofen-induced GIRK current from Ts65Dn neurons indicated no significant change in single-channel conductance compared with diploid. However, significant increases in GIRK channel density was found in Ts65Dn neurons. In normalized baclofen-induced GIRK current and GIRK current kinetics no difference was found between diploid and Ts65Dn neurons, which suggests unimpaired mechanisms of interaction between GIRK channel and GABA(B) receptor. These results indicate that increased expression of GIRK2 containing channels have functional consequences that likely affect the balance between excitatory and inhibitory neuronal transmission.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Baclofen,
http://linkedlifedata.com/resource/pubmed/chemical/G Protein-Coupled...,
http://linkedlifedata.com/resource/pubmed/chemical/GABA Agonists,
http://linkedlifedata.com/resource/pubmed/chemical/Kcnj6 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Potassium,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, GABA-B,
http://linkedlifedata.com/resource/pubmed/chemical/gamma-Aminobutyric Acid
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jan
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| pubmed:issn |
0022-3077
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
97
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
892-900
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| pubmed:dateRevised |
2007-12-3
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| pubmed:meshHeading |
pubmed-meshheading:17093127-Animals,
pubmed-meshheading:17093127-Animals, Newborn,
pubmed-meshheading:17093127-Baclofen,
pubmed-meshheading:17093127-Brain,
pubmed-meshheading:17093127-Cell Membrane,
pubmed-meshheading:17093127-Cells, Cultured,
pubmed-meshheading:17093127-Disease Models, Animal,
pubmed-meshheading:17093127-Dose-Response Relationship, Drug,
pubmed-meshheading:17093127-Down Syndrome,
pubmed-meshheading:17093127-Excitatory Postsynaptic Potentials,
pubmed-meshheading:17093127-G Protein-Coupled Inwardly-Rectifying Potassium Channels,
pubmed-meshheading:17093127-GABA Agonists,
pubmed-meshheading:17093127-Inhibitory Postsynaptic Potentials,
pubmed-meshheading:17093127-Mice,
pubmed-meshheading:17093127-Mice, Neurologic Mutants,
pubmed-meshheading:17093127-Neurons,
pubmed-meshheading:17093127-Patch-Clamp Techniques,
pubmed-meshheading:17093127-Potassium,
pubmed-meshheading:17093127-Receptors, GABA-B,
pubmed-meshheading:17093127-Synaptic Transmission,
pubmed-meshheading:17093127-Trisomy,
pubmed-meshheading:17093127-gamma-Aminobutyric Acid
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| pubmed:year |
2007
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| pubmed:articleTitle |
Ts65Dn, a mouse model of Down syndrome, exhibits increased GABAB-induced potassium current.
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| pubmed:affiliation |
Neuroscience Graduate Program, School of Medicine, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd., Bethesda, MD 20814, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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