Release of [3H]L-glutamate and [3H]L-glutamine in rat cerebellum slices: a comparison of the effect of veratridine and electrical stimulation.

Depolarization-elicited release of neurotransmitter glutamate was studied in rat cerebellar slices previously loaded with either [3H]L-glutamate or [3H]L-glutamine. Both depolarization conditions used (e.g. long-lasting tonic depolarization elicited by veratridine, or short repetitive electrical pulses) increased 6 to 8 folds the release of labelled glutamate and of another compound, presumably alpha-ketoglutarate, without modifying the release of labeled glutamine. Because of the position of the label in the precursor radioactive molecules, GABA was weakly labeled and aspartate was unlabeled. The properties of the evoked glutamate release from cerebellar slices were those of a neurotransmitter since it was inhibited by tetrodotoxin and was Ca2+-dependent. Alpha-ketoglutarate is either coreleased from nerve terminals or is released from astrocytes and could participate in glutamate recycling. The data confirm the generally accepted model implying the presence of two neurotransmitter glutamate pools, a neuronal pool of newly synthesized glutamate and an astrocytic storage pool, but in addition indicate that the former is in rapid isotopic equilibrium with the extracellular compartment. Our present results also indicate that the glutamate/glutamine cycle is not activated in depolarizing conditions.