Chapter 19 Structure and function of sodium-coupled amino acid neurotransmitter transporters

Abstract

Publisher Summary Sodium-coupled neurotransmitter transporters, located in the plasma membrane of nerve terminals and glial processes, serve to keep the extracellular transmitter levels below those that are neurotoxic. They help, in conjunction with diffusion, to terminate its action in synaptic transmission. Such a termination mechanism operates with most transmitters, including γ-aminobutyric acid (GABA), L-glutamate, glycine, dopamine, serotonin, and norepinephrine. Another termination mechanism is observed with cholinergic transmission. After dissociation from its receptor, acetylcholine is hydrolyzed into choline and acetate. The choline moiety is then recovered by sodium-dependent transport. As the concentration of the transmitters in the nerve terminals is much higher than in the cleft—typically by four orders of magnitude—energy input is required. The transporters that are located in the plasma membranes of nerve endings and glial cells obtain this energy by coupling the flow of neurotransmitters to that of sodium. The (Na + + K + )-ATPase generates an inwardly-directed electrochemical sodium gradient, which is utilized by the transporters to drive uphill transport of the neurotransmitters. Neurotransmitter uptake systems are investigated by using plasma membranes obtained upon osmotic shock of synaptosomes. It appears that these transporters are coupled not only to sodium, but also to additional ions, such as potassium or chloride.