Neurotransmitter transporters are a class ofmembrane transport proteins that span thecellular membranes of neurons. Their primary function is to carryneurotransmitters across these membranes and to direct their further transport to specific intracellular locations. There are more than twenty types of neurotransmitter transporters.[1]
Vesicular transporters move neurotransmitters intosynaptic vesicles, regulating the concentrations of substances within them.[2] Vesicular transporters rely on aproton gradient created by thehydrolysis ofadenosine triphosphate (ATP) in order to carry out their work:v-ATPase hydrolyzes ATP, causing protons to be pumped into thesynaptic vesicles and creating a proton gradient. Then the efflux of protons from the vesicle provides the energy to bring the neurotransmitter into the vesicle.[3]
Neurotransmitter transporters frequently useelectrochemical gradients that exist across cell membranes to carry out their work. For example, some transporters use energy obtained by thecotransport, orsymport, ofNa+ in order to moveglutamate across membranes. Such neurotransporter cotransport systems are highly diverse, as recent development indicates that uptake systems are generally selective and associate with a specific neurotransmitter.[4]
Normally, transporters in thesynaptic membrane serve to remove neurotransmitters from the synaptic cleft and prevent their action or bring it to an end. However, on occasion transporters can work in reverse, transporting neurotransmitters into the synapse, allowing these neurotransmitters to bind to theirreceptors and exert their effect. This "nonvesicular release" of neurotransmitters is used by some cells, such asamacrine cells in theretina, as a normal form of neurotransmitter release.[5]
Specific types of neurotransmitter transporters include the following:
Note that there is no plasmalemmalacetylcholine transporter, as acetylcholine is terminated via rapid metabolism intocholine bycholinesteraseenzymes, and choline is subsequently transported back into the cell and reconverted into acetylcholine.
Transporters associated withhistamine and theendocannabinoids have not yet been identified.
A variety of neurotransmitter reuptake transporters are pharmacotherapeutic targets for modulating the synaptic neurotransmitter concentration, and therefore neurotransmission.
Vesicular transporters could provide an alternative therapeutic target for the modulation of chemical neurotransmission, as the activity of these transporters could affect the quantity of neurotransmitter released.[7]
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