GABAA autoreceptors enhance GABA release from human neocortex: towards a mechanism for high-frequency stimulation (HFS) in brain?
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High-frequency stimulation (HFS) in human neocortical slices induces γ-aminobutyric acid (GABA) release via GABAA receptor (GABAAR) activation. The mechanism of this effect and the localization of these GABAARs were now studied. Fresh human neocortical slices were subjected to HFS (130 Hz) in the presence of veratridine (3 µM). 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 GABAARs are localized on soma and dendrites of GABAergic neurons in the human neocortex. Moreover, in support of a terminal localization of GABAARs, the K+-evoked [3H]-GABA release from synaptosomes was enhanced by the GABAAR agonist muscimol (antagonized by GABAAR blockers). We conclude that HFS in human brain neocortex leads to a specific increase of GABA release, which is mediated by facilitatory GABAA autoreceptors located on soma, dendrites, and axon terminals of GABAergic neurons.
KeywordsHigh-frequency stimulation Potassium depolarization γ-aminobutyric acid (GABA) release GABAA autoreceptor localization Human neocortex slices Human neocortex synaptosomes
artificial cerebrospinal fluid
glutamic acid decarboxylase
1-diphenylmethyleneaminooxyethyl-l,2,5,6-tetrahydro-3-pyridinecarboxylic acid hydrochloride
(±) nipecotic acid
M. M. gratefully acknowledges the support by the German Academic Exchange Service (DAAD).
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