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A kinetic analysis of the release of acidic amino acids from rat cortical synaptosomes following pre-loading with [14C]glutamic acid

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Abstract

The kinetics of the release of acidic amino acids have been studied in rat cortical synaptosomes. After pre-loading for 30 minutes in labeled glutamate, labeled glutamate and aspartate appear to be totally releasable. However, extra-synaptosomal Ca does not facilitate release. When elevated [K]0 was used to depolarize, release was unaffected by removal of Ca from the incubation medium. When veratridine was used as a depolarizing agent, presence of Ca in the incubation medium inhibited release. In all solutions, semi-log plots of synaptosomal label content as a function of time were non-linear, which is incompatible with release from a single compartment. Previous studies of the effect of membrane potential on transport led to the development of a carrier model which should participate in depolarization induced release (19). Under the conditions used in the present studies, this carrier should be saturated. When the data were fitted to a two compartment model, with release from compartment A linear with compartment size and release from compartment B via a saturated carrier, an excellent fit was obtained. Under control conditions, about 90% of the labeled amino acid is in compartment B and about 70% of the total release is from this compartment. Rate of release is greatly accelerated in depolarizing solutions. Under depolarizing conditions, there is a large shift of labeled amino acid from compartment B to compartment A and release from compartment A predominates. Analysis of the results under the several depolarizing conditions used shows that the present results are consistent with the predictions of the carrier model which has been developed from previous studies of the Na and membrane potential dependence of glutamate transport.

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Wheeler, D.D., Wise, W.C. A kinetic analysis of the release of acidic amino acids from rat cortical synaptosomes following pre-loading with [14C]glutamic acid. Neurochem Res 8, 1111–1134 (1983). https://doi.org/10.1007/BF00964926

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