Are GAD65 and GAD67 associated with specific pools of GABA in brain?

Abstract

Brain contains at least two pools of gamma-aminobutyric acid (GABA), the transmitter pool and the so-called metabolic pool. To a large extent these pools may reflect the presence of GABA in different intracellular compartments, as immunocytochemical studies show that GABA is not localized mainly in terminals but is distributed throughout neurons. An interesting issue is the extent to which the two major forms of glutamate decarboxylase (GAD65 and GAD67) are specialized to synthesize GABA for these pools. Although GAD65 and GAD67 differ significantly in several characteristics, they also have substantial similarities and interactions, and the presence of individual forms of GAD in certain cell types is consistent with the idea that GAD65 and GAD67 can each synthesize GABA for both pools. Substantial progress has been made in understanding the regulatory properties of GAD, but the available data provide little indication of how differences between the forms might enable each to serve the demands for GABA synthesis in a specific pool.