ABSTRACT
The inactivation of GABA, the major inhibitory neurotransmitter in the CNS (Roberts, 1991), is brought about by diffusion away from the receptors followed by high affinity transport into the presynaptic GABAergic neuron as well as surrounding astroglial cells (Schousboe, 1981, 1990). Analysis of the kinetic characteristics of GABA transport in a variety of preparations of neurons and astrocytes has led to the proposal that at GABAergic synapsis by far the majority of the released GABA is taken up back into the GABAergic nerve endings allowing GABA to be recycled as neurotransmitter (Hertz and Schousboe, 1987). Thus only about 20 per cent of the released GABA will be lost as a neurotransmitter by uptake into surrounding astrocytes, where it is metabolized via GABA-transaminase, succinate semialdehyde dehydrogenase and the TCA cycle to CO2 (Schousboe, 1981; Hertz and Schousboe, 1987). On the basis of these considerations it has been proposed that the activity of the astrocytic GABA transporters may be of critical importance for the efficacy of the GABA neurotransmission; hence the elucidation of the pharmacological properties of neuronal and glial GABA transport systems has become of interest (Schousboe, 1990). The advent of the cloning of a number of GABA transporters (Guastella et al., 1990; Lopéz-Corcuera et al., 1992; Liu et al., 1992, 1993; Clark et al., 1992; Borden et al., 1992, 1994, 1995; Borden, 1996) has provided the tools to investigate in closer detail the distribution, molecular properties and function of the GABA transporters. Moreover, the availability of a variety of GABA analogs of restricted conformation has further facilitated the study of the pharmacological properties of these transporters (Krogsgaard-Larsen et al., 1987; Schousboe et al., 1991; Falch et al., 1999). This review will concentrate on providing an update on these aspects.
