Sodium-Coupled Neurotransmitter Transporters

Abstract

Sodium-coupled neurotransmitter transporters are located in the plasma membranes of neurons and glia, where they are present at high density in those areas of the cell membrane that face the synapse (Figure 1). They serve to keep the extracellular neurotransmitter concentrations sufficiently low, so that the postsynaptic receptors are able to detect signaling by the presynaptic nerve cell in the form of exocytotically released transmitters (Figure 1). Thus, neurotransmitter transporters are key elements in the termination of the synaptic actions of neurotransmitters. Moreover, they serve to keep the extracellular transmitter concentrations below neurotoxic levels. Termination of synaptic transmission by transporters takes place with most neurotransmitters, including L-glutamate, γ-aminobutyric acid (GABA), 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. Even then, the choline moiety is subsequently recovered by sodium-dependent transport. Because the concentration of the transmitters in the nerve terminals is orders of magnitude higher than that in the synaptic cleft, energy input is required to move the neurotransmitters against their concentration gradients. The transporters, located * To whom correspondence should be addressed. Telephone: +972-26758506. Fax: +972-2-6757379. E-mail: kannerb@cc.huji.ac.il. Baruch I. Kanner was born on January 8, 1947. He earned his B.Sc. degree in chemical technology from Technological University, Delft, The Netherlands, in 1968, his M.Sc. degree in biochemistry from Technological University, Delft, The Netherlands, in 1969, and his Ph.D. degree in microbiology from Tel Aviv University, Tel Aviv, Israel, in 1974. He performed his postdoctoral work at Cornell University, Ithaca, NY, with Efraim Racker from 1974-1976. He was a Lecturer in Biochemistry at Hebrew University, Jerusalem, Israel, from 1976-1979, a Senior Lecturer in Biochemistry at Hebrew University, Jerusalem, Israel, from 1979-1983, an Associate Professor of Biochemistry at Hebrew University, Jerusalem, Israel, from 1983-1990, and a Professor of Biochemistry at Hebrew University, Jerusalem, Israel, from 1990-present.