The present study investigates the effects of
phenylsuccinate (PS), an inhibitor of the mitochondrial ketodicarboxylate carrier (KCC), on release ofγ-
aminobutyric acid (
GABA),
glutamate (Glu),
glutamine (Gln), and
glycine (Gly), induced by
potassium chloride (KCl) and by
cardiac arrest caused by a
halothane overdose. Microdialysates were collected from the hippocampus of anaesthetized rats, and analyzed by HPLC. Continuous perfusion of 50 mM PS through the dialysis probe, reduces release of
GABA induced by KCl (50 mM for 10 min through the dialysis probe) by up to 72%. In addition, PS abolished KCl-induced release of Glu. Release of
GABA during
cardiac arrest was not reduced by PS, whereas PS reduced release of Glu in the early stage of
cardiac arrest. PS furthermore increased the basal level of Gln, and reversed a decrease of Gln induced by
cardiac arrest.It is proposed that the KCC is present in
GABA'ergic neurons of the rat hippocampus, and that
GABA, released by KCl, can be synthesized in a KCC dependent manner. It is also suggested that
ischemia-induced release of
GABA, to some extent, has a non-transmitter origin. The results furthermore indicate that uptake of Gln into
GABA'ergic and Glu'ergic neurons is not regulated by simple demand mechanisms.