THE FAMILY OF NA+ CL- NEUROTRANSMITTER TRANSPORTERS/

The termination of neurotransmission is achieved by rapid uptake of th e released neurotransmitter by specific high-affinity neurotransmitter transporters. Most of these transporters are encoded by a family of g enes (Na+/Cl- transporters) having a similar membrane topography of 12 transmembrane helices. An evolutionary tree revealed five distinct su bfamilies: gamma-aminobutyric acid transporters, monoamine transporter s, amino acid transporters, ''orphan'' transporters, and the recently discovered bacterial transporters. The bacterial transporters that bel ong to this family may help to develop heterologous expression systems with the aim of solving the three-dimensional structure of these memb rane proteins. Some of the neurotransmitter transporters have been imp licated as important sites for drug action. Monoamine transporters, fo r example, are targeted by major classes of antidepressants, psychosti mulants, and antihypertensive drugs. Localization of individual transp orters in specific cells and brain areas is pertinent to understanding their contribution to neurotransmission and their potential as target s for drugs. The most important questions in the field include resolvi ng the mechanism of neurotransmitter transport, the structure of the t ransporters, and the interaction of each transporter in complex neurol ogical activities.