Structure and function of sodium-coupled GABA and glutamate transporters

Neurotransmitter transporters are key elements in the termination of the synaptic actions of the neurotransmitters. They use the energy stored in the electrochemical ion gradients across the plasma membrane of neurons and glial cells for uphill transport of the transmitters into the cells surrounding the synapse. Therefore specific transporter inhibitors can potentially be used as novel drugs for neurological disease. Sodium-coupled neurotransmitter transporters belong to either of two distinct families. The glutamate transporters belong to the SLC1 family, whereas the transporters of the other neurotransmitters belong to the SLC6 family. An exciting and recent development is the emergence of the first high-resolution structures of archeal and bacterial members belonging to these two families. In this review the functional results on prototypes of the two families, the GABA transporter GAT-1 and the glutamate transporters GLT-1 and EAAC1, are described and discussed within the perspective provided by the novel structures.