Na(+)-dependent GABA transport system scavenges endogenous external GABA and prevents desensitization of GABAA receptors in rat cerebrocortical synaptoneurosomes
| Autor: | David P. Blakeman, Wha Bin Im, J.P. Davis |
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| Rok vydání: | 1990 |
| Předmět: |
Male
medicine.medical_specialty Proline medicine.medical_treatment Population Nipecotic Acids Endogeny Ouabain chemistry.chemical_compound Chlorides Internal medicine Nipecotic acid medicine Animals Neurotransmitter Uptake Inhibitors Receptor education Electrochemical gradient Molecular Biology gamma-Aminobutyric Acid Desensitization (medicine) Cerebral Cortex education.field_of_study GABAA receptor Muscimol General Neuroscience Sodium Rats Inbred Strains Receptors GABA-A Rats Endocrinology nervous system chemistry Biophysics Neurology (clinical) Developmental Biology medicine.drug Synaptosomes |
| Zdroj: | Brain research. 521(1-2) |
| ISSN: | 0006-8993 |
| Popis: | Muscimol-induced 36Cl- uptake in rat cerebrocortical synaptoneurosomes was reduced upon exposure of the membrane sacs to low Na+ media. This Na+ requirement led us to examine the role of the Na(+)-dependent gamma-aminobutyric acid (GABA) transport system in 36Cl- uptake. Incubation of the synaptoneurosomes with nipecotic acid, a specific inhibitor of the GABA transport system, for 10 min increased the level of endogenous external GABA from less than 10 to 150 microM and induced the same signs of desensitization as observed with high muscimol-treated synaptoneurosomes; a marked reduction of muscimol-induced 36Cl- uptake and an appearance of a slow bicuculline-sensitive 36Cl- uptake, probably due to a continuous recovery of a population of GABAA receptors from desensitization. Similar results were obtained upon dissipation of Na+ electrochemical gradient across the membranes by inhibition of Na+, K(+)-ATPase with ouabain or by blocking energy metabolism with azide or N-ethylmaleimide. We propose that the Na(+)-dependent GABA transport system, its operation being dependent on inwardly directed Na+ electrochemical gradient, is responsible for scavenging endogenous GABA released from the synaptoneurosomes, and thus prevents desensitization of GABAA receptors. |
| Databáze: | OpenAIRE |
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