Functional assessment of GABA uptake or exchange by synaptosomal fractions

THE discovery of a transport system in nervous tissue for an amino acid with an apparent K_m equal to or less than 10^-5 M has been taken as support of a neurotransmitter function for this compound. "High affinity" systems of this sort have been described for γ-amino butyric acid (GABA)¹, glutamate², glycine³, aspartate⁴ and taurine⁵. Initially it was hoped that such transmitter transport systems could be used to map the utilisation of a given transmitter in defined anatomical regions. Unfortunately nonspecific elements, especially glial cells, also have the capacity to transport neurotransmitter candidates using "high affinity" systems⁶. Furthermore, Levi and Raiteri⁷, noting that "high affinity" transport was found where the internal concentration of the amino acid was high, suggested that isotopic measurements of inward transport were misleading and that exchange of labelled amino acid for unlabelled amino acid is likely to be the phenomena that has been measured⁸. This called into question the functional role of "high affinity" transport systems, and has resulted in considerable controversy⁹. In an effort to clarify the conditions of amino acid uptake, we have measured net GABA movement in nerve-terminal-enriched fractions¹⁰.