In vitro release of endogenous amino acids from granule cell-, stellate cell-, and climbing fiber-deficient cerebella.

Abstract

The K+-stimulated, Ca2+-dependent release of glutamate, aspartate, gamma-aminobutyric acid (GABA), alanine, taurine, and glycine was measured in slices of cerebella obtained from control, and granule cell-, granule cell plus stellate cell-, or climbing fiber-deficient cerebella of the rat. The 55 mM-K+-stimulated release of glutamate and GABA was 10-fold greater in the presence of Ca2+ than in its absence. The stimulated release of aspartate was 4-fold higher when Ca2+ was present in the bathing media, while the value for alanine was twice as high as the amount obtained in the absence of Ca2+. There was no stimulated release of either taurine or glycine from the cerebellar slices. Increasing the Mg2+ concentration to 16 mM inhibited the K+-stimulated, Ca2+-dependent release of glutamate, GABA, aspartate, and alanine 85% or more. The K+-stimulated, Ca2+ dependent release of glutamate, aspartate, and alanine from x-irradiated cerebella deficient in granule cells was reduced to 50-57% of control value. Additional x-irradiation treatment, which further reduced the cerebellar granule cell population and also prevented the acquisition of stellate cells, decreased the release of glutamate by 77%, aspartate by 66%, alanine by 91%, and, in addition, decreased the release of GABA by 55%. The K+-stimulated, Ca2+-dependent release of glutamate, aspartate, GABA, and alanine was not changed in climbing fiber-deficient cerebella obtained from 3-acetylpyridine-treated rats. The data support a transmitter role for GABA and glutamate in the cerebellum, but do not support a similar function for either taurine or glycine. The data also suggest that alanine and aspartate may be co-released along with glutamate from granule cells.