Publication Date:
1995-08-18
Description:
Gamma-aminobutyric acid A (GABAA) receptors are the principal mediators of synaptic inhibition, and yet when intensely activated, dendritic GABAA receptors excite rather than inhibit neurons. The membrane depolarization mediated by GABAA receptors is a result of the differential, activity-dependent collapse of the opposing concentration gradients of chloride and bicarbonate, the anions that permeate the GABAA ionophore. Because this depolarization diminishes the voltage-dependent block of the N-methyl-D-aspartate (NMDA) receptor by magnesium, the activity-dependent depolarization mediated by GABA is sufficient to account for frequency modulation of synaptic NMDA receptor activation. Anionic gradient shifts may represent a mechanism whereby the rate and coherence of synaptic activity determine whether dendritic GABAA receptor activation is excitatory or inhibitory.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Staley, K J -- Soldo, B L -- Proctor, W R -- AA03527/AA/NIAAA NIH HHS/ -- HD27827/HD/NICHD NIH HHS/ -- NS01573/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 1995 Aug 18;269(5226):977-81.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurology, University of Colorado Health Sciences Center, Denver 80262, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7638623" target="_blank"〉PubMed〈/a〉
Keywords:
Acetazolamide/pharmacology
;
Amiloride/pharmacology
;
Animals
;
Bicarbonates/*metabolism
;
Chlorides/*metabolism
;
Dendrites/metabolism
;
Hydrogen-Ion Concentration
;
In Vitro Techniques
;
Magnesium/pharmacology
;
Membrane Potentials
;
Muscimol/pharmacology
;
Neurons/*metabolism
;
Pyramidal Cells/metabolism
;
Rats
;
Receptors, GABA-A/*metabolism
;
Receptors, N-Methyl-D-Aspartate/metabolism
;
Synapses/metabolism
;
gamma-Aminobutyric Acid/*metabolism/pharmacology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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