Abstract
GABA is known to be the inhibitory neurotransmitter in the majority of brain stem nuclei. The release of GABA has been extensively studied both in vivo and in vitro in higher brain areas, whereas the mechanisms of release in the brain stem have not been systemically characterized. The properties of preloaded [3H]GABA were now investigated in mouse brain stem slices, using a superfusion system. The basal release was enhanced by K+ stimulation (50 mM K+) and under various cell-damaging conditions (ischemia, hypoglycemia, the presence of free radicals and metabolic poisons). No K+-stimulated release was discernible in the absence of Ca2+, indicating that the release was at least partly Ca2+-dependent. Moreover, the release was increased when Na+ or Cl- was omitted from the superfusion medium. GABA and beta-alanine stimulated the release, confirming the involvement of the reversed function of GABA transporters. Incubation of the slices with the anion channel inhibitors diisothiocyanostilbene and 4-acetamido-4'-isothiocyanostilbene-2,2'-disulphonate and with the Cl- uptake inhibitor 9-anthracenecarboxylic acid also reduced GABA release, demonstrating that a part of it comprises leakage through anion channels. All these mechanisms were involved in the ischemia-induced GABA release, which was over 4-fold greater than the release in normoxia. Contrary to the other brain areas, GABA release in the brain stem was not affected by ionotropic glutamate receptors but may be modulated by metabotropic receptors. This ischemia-induced GABA release might constitute an important mechanism against excitotoxicity, protecting the brain stem under cell-damaging conditions.
Published Version
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