Switch to
Predicate | Object |
---|---|
rdf:type | |
lifeskim:mentions | |
pubmed:issue |
7
|
pubmed:dateCreated |
1998-4-7
|
pubmed:abstractText |
Although GABA type A receptors (GABAARs) in principal cells have been studied in detail, there is only limited information about GABAARs in interneurons. We have used the patch-clamp technique in acute rat hippocampal slices in combination with single-cell PCR to determine kinetic, pharmacological, and structural properties of dentate gyrus basket cell GABAARs. Application of 1 mM GABA (100 msec) to nucleated patches via a piezo-driven fast application device resulted in a current with a fast rise and a marked biexponential decay (time constants 2.4 and 61.8 msec). This decay could be attributed to strong receptor desensitization. Dose-response curves for the peak and the slow component yielded EC50 values of 139 and 24 microM, respectively. Zn2+ caused a marked blocking effect on both the peak and the slow component via a noncompetitive mechanism (IC50 values of 8 and 16 microM). This led to an acceleration of the slow component as well as a prolongation of recovery from desensitization. Zn2+ sensitivity was suggested to depend on the absence of gamma-subunits in GABAARs. To test this hypothesis we performed single-cell reverse transcription PCR that revealed primarily the presence of alpha2-, beta2-, beta3-, gamma1-, and gamma2-subunit mRNAs. In addition, flunitrazepam increased the receptor affinity for its agonist, indicating the presence of functional benzodiazepine binding sites, i.e., gamma-subunits. Thus, additional factors seem to co-determine the Zn2+ sensitivity of native GABAARs. The modulatory effects of Zn2+ on GABAAR desensitization suggest direct influences on synaptic integration via changes in inhibition and shunting at GABAergic synapses.
|
pubmed:language |
eng
|
pubmed:journal | |
pubmed:citationSubset |
IM
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Flunitrazepam,
http://linkedlifedata.com/resource/pubmed/chemical/GABA Agents,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, GABA-A,
http://linkedlifedata.com/resource/pubmed/chemical/Zinc,
http://linkedlifedata.com/resource/pubmed/chemical/gamma-Aminobutyric Acid
|
pubmed:status |
MEDLINE
|
pubmed:month |
Apr
|
pubmed:issn |
0270-6474
|
pubmed:author | |
pubmed:issnType |
Print
|
pubmed:day |
1
|
pubmed:volume |
18
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
2437-48
|
pubmed:dateRevised |
2006-11-15
|
pubmed:meshHeading |
pubmed-meshheading:9502804-Animals,
pubmed-meshheading:9502804-Dentate Gyrus,
pubmed-meshheading:9502804-Dose-Response Relationship, Drug,
pubmed-meshheading:9502804-Flunitrazepam,
pubmed-meshheading:9502804-GABA Agents,
pubmed-meshheading:9502804-Gene Expression,
pubmed-meshheading:9502804-Ion Channel Gating,
pubmed-meshheading:9502804-Kinetics,
pubmed-meshheading:9502804-Patch-Clamp Techniques,
pubmed-meshheading:9502804-Polymerase Chain Reaction,
pubmed-meshheading:9502804-RNA, Messenger,
pubmed-meshheading:9502804-Rats,
pubmed-meshheading:9502804-Rats, Wistar,
pubmed-meshheading:9502804-Receptors, GABA-A,
pubmed-meshheading:9502804-Zinc,
pubmed-meshheading:9502804-gamma-Aminobutyric Acid
|
pubmed:year |
1998
|
pubmed:articleTitle |
Dentate gyrus basket cell GABAA receptors are blocked by Zn2+ via changes of their desensitization kinetics: an in situ patch-clamp and single-cell PCR study.
|
pubmed:affiliation |
Institute of Physiology, University of Freiburg, D-79104 Freiburg, Germany.
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|