Neurotransmitter transporters frequently use electrochemical gradients that exist across cell membranes to carry out their work. For example, some transporters use energy obtained by the cotransport, or symport, of Na+ in order to move glutamate 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.
Normally, transporters in the synaptic 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 their receptors and exert their effect. This "nonvesicular release" of neurotransmitters is used by some cells, such as amacrine cells in the retina, as a normal form of neurotransmitter release.
Note that there is no plasmalemmal acetylcholine transporter, as acetylcholine is terminated via rapid metabolism into choline by cholinesteraseenzymes, and choline is subsequently transported back into the cell and reconverted into acetylcholine.
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.