Document Detail

GABA(A) autoreceptors enhance GABA release from human neocortex: towards a mechanism for high-frequency stimulation (HFS) in brain?
MedLine Citation:
PMID:  19296090     Owner:  NLM     Status:  MEDLINE    
High-frequency stimulation (HFS) in human neocortical slices induces gamma-aminobutyric acid (GABA) release via GABA(A) receptor (GABA(A)R) activation. The mechanism of this effect and the localization of these GABA(A)Rs were now studied. Fresh human neocortical slices were subjected to HFS (130 Hz) in the presence of veratridine (3 microM). As measured by high-performance liquid chromatography, only GABA but not glutamate outflow was affected by HFS/veratridine stimulation. The evoked GABA overflow was abolished by tetrodotoxin and furosemide, suggesting an involvement of action potentials and plasmalemmal chloride gradients. Double immunolabeling showed that GABA(A)Rs are localized on soma and dendrites of GABAergic neurons in the human neocortex. Moreover, in support of a terminal localization of GABA(A)Rs, the K+-evoked [3H]-GABA release from synaptosomes was enhanced by the GABA(A)R agonist muscimol (antagonized by GABA(A)R blockers). We conclude that HFS in human brain neocortex leads to a specific increase of GABA release, which is mediated by facilitatory GABA(A) autoreceptors located on soma, dendrites, and axon terminals of GABAergic neurons.
Michela Mantovani; Andreas Moser; Carola A Haas; Josef Zentner; Thomas J Feuerstein
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-03-19
Journal Detail:
Title:  Naunyn-Schmiedeberg's archives of pharmacology     Volume:  380     ISSN:  1432-1912     ISO Abbreviation:  Naunyn Schmiedebergs Arch. Pharmacol.     Publication Date:  2009 Jul 
Date Detail:
Created Date:  2009-05-15     Completed Date:  2009-07-13     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0326264     Medline TA:  Naunyn Schmiedebergs Arch Pharmacol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  45-58     Citation Subset:  IM    
Section of Clinical Neuropharmacology, Department of Neurosurgery, University Hospital Freiburg, Breisacherstrasse 64, 79106 Freiburg, Germany.
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MeSH Terms
Action Potentials*
Autoreceptors / metabolism
Child, Preschool
Chromatography, High Pressure Liquid
Electric Stimulation*
Middle Aged
Neocortex / metabolism
Neurons / metabolism
Receptors, GABA-A / metabolism*
Veratridine / pharmacology
Young Adult
gamma-Aminobutyric Acid / metabolism*
Reg. No./Substance:
0/Autoreceptors; 0/Receptors, GABA-A; 56-12-2/gamma-Aminobutyric Acid; 71-62-5/Veratridine

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