Linked Life Data

2157838

Source:http://linkedlifedata.com/resource/pubmed/id/2157838

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
1990-5-24
pubmed:abstractText
1. Current mediated by GABAA receptors was examined in pyramidal cells acutely dissociated from the hippocampus of mature guinea-pigs. Current responses were measured using whole-cell voltage-clamp recordings. An internal perfusion technique was used to change the intracellular contents during recording. 2. Application of GABA (100-300 microM) by short duration pressure pulses produced outward current responses at a holding potential of -10 mV. When recordings were made with intracellular solutions which did not contain Mg-ATP, GABA responses progressively decreased to less than 10% of their initial values after 10 min. This 'run-down' of the GABA response could not be accounted for by desensitization since the rate of run-down was not dependent upon agonist application. 3. The run-down of the GABAA response was reversed when Mg2+ (4 mM) and ATP (2 mM) were introduced into the intracellular perfusate. In addition to the presence of Mg-ATP, buffering of Ca2+ in the intracellular solution to low levels (approximately 10(-8) M) was also necessary to stabilize the GABAA response. 4. The role of a phosphorylation process in regulating the GABAA receptor was tested. After the GABA response stabilized, introduction of alkaline phosphatase (100 micrograms/ml) to the intracellular perfusate caused a complete run-down of the GABA response. 5. Stable GABA responses were obtained when ATP was replaced by ATP-gamma-S (adenosine 5'-O-(thiotriphosphate), an analogue of ATP that donates a thiophosphate group resulting in a product that is more resistant to hydrolysis. Following such treatment GABA responses declined more slowly after the introduction of intracellular alkaline phosphatase. 6. Run-down of GABA responses accelerated when intracellular Ca2+ concentration ([Ca2+]i) was elevated to about 5 x 10(-4) M. The run-down caused by elevated [Ca2+]i could be stopped and reversed by reducing [Ca2+]i to about 10(-8) M. 7. The introduction of ATP-gamma-S to the intracellular medium retarded the run-down of GABA responses caused by elevation of [Ca2+]i. 8. N-(6-Aminohexyl)-5-chloro-1-naphthalenesulphonamide (W-7), a calmodulin inhibitor, reduced the rate of run-down induced by elevated [Ca2+]i. 9. These results suggest that the function of the GABAA receptor is maintained by phosphorylation of the receptor or some closely associated regulatory molecule. Elevation of [Ca2+]i destabilizes the function of the GABAA receptor, probably by activating a Ca2+/calmodulin-dependent phosphatase.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/2157838-14012800, http://linkedlifedata.com/resource/pubmed/commentcorrection/2157838-2411211, http://linkedlifedata.com/resource/pubmed/commentcorrection/2157838-2420980, http://linkedlifedata.com/resource/pubmed/commentcorrection/2157838-2431316, http://linkedlifedata.com/resource/pubmed/commentcorrection/2157838-2432251, http://linkedlifedata.com/resource/pubmed/commentcorrection/2157838-2436233, http://linkedlifedata.com/resource/pubmed/commentcorrection/2157838-2437114, http://linkedlifedata.com/resource/pubmed/commentcorrection/2157838-2442720, http://linkedlifedata.com/resource/pubmed/commentcorrection/2157838-2455347, http://linkedlifedata.com/resource/pubmed/commentcorrection/2157838-2456612, http://linkedlifedata.com/resource/pubmed/commentcorrection/2157838-2646715, http://linkedlifedata.com/resource/pubmed/commentcorrection/2157838-2709096, http://linkedlifedata.com/resource/pubmed/commentcorrection/2157838-2843609, http://linkedlifedata.com/resource/pubmed/commentcorrection/2157838-2849041, http://linkedlifedata.com/resource/pubmed/commentcorrection/2157838-293720, http://linkedlifedata.com/resource/pubmed/commentcorrection/2157838-2982363, http://linkedlifedata.com/resource/pubmed/commentcorrection/2157838-2984352, http://linkedlifedata.com/resource/pubmed/commentcorrection/2157838-3004820, http://linkedlifedata.com/resource/pubmed/commentcorrection/2157838-3010675, http://linkedlifedata.com/resource/pubmed/commentcorrection/2157838-3523050, http://linkedlifedata.com/resource/pubmed/commentcorrection/2157838-3542117, http://linkedlifedata.com/resource/pubmed/commentcorrection/2157838-3670374, http://linkedlifedata.com/resource/pubmed/commentcorrection/2157838-6244050, http://linkedlifedata.com/resource/pubmed/commentcorrection/2157838-6270629, http://linkedlifedata.com/resource/pubmed/commentcorrection/2157838-6282187, http://linkedlifedata.com/resource/pubmed/commentcorrection/2157838-6292777, http://linkedlifedata.com/resource/pubmed/commentcorrection/2157838-6301828, http://linkedlifedata.com/resource/pubmed/commentcorrection/2157838-6389184, http://linkedlifedata.com/resource/pubmed/commentcorrection/2157838-6897280, http://linkedlifedata.com/resource/pubmed/commentcorrection/2157838-7131309, http://linkedlifedata.com/resource/pubmed/commentcorrection/2157838-7143035
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0022-3751
pubmed:author
pubmed:issnType
Print
pubmed:volume
420
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
207-21
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed:year
1990
pubmed:articleTitle
GABAA receptor function is regulated by phosphorylation in acutely dissociated guinea-pig hippocampal neurones.
pubmed:affiliation
Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY 10032.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't