Vesicular GABA Transporters

GABA is packaged into vesicles at the synapse by the vesicular GABA transporter (vGAT), which was recently cloned. Although vGAT transports GABA across a membrane, it bears no resemblance to the GATs. Both the amino and carboxy termini of vGAT are cytoplasmic, and there are 10 predicted transmembrane domains (Fig. 8).

vGAT, with a Km for GABA in the millimolar range, depends on both pH and electrochemical gradients (DpH and DC) across the vesicular membrane to concentrate GABA into vesicles. These gradients are maintained by Mg2 + -activated ATPase, which belongs to the class of vacuolar ATPases. Vesicular transporters for other neurotransmitters have a different dependence on the same gradients. For instance, the vesicular dopamine transporter depends mostly on

DpH, whereas the vesicular glutamate transporter depends mostly on DC.

Glycine, an inhibitory neurotransmitter, can also be transported by vGAT. vGAT mRNA distribution in neurons coincides with other glycinergic and GA-BAergic markers. Immunohistochemical studies demonstrate vGAT in terminals and the neurotransmitter phenotype of the particular terminals can be GABA, glycine, or mixed.

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