Neurotransmitter transporter

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Neurotransmitter transporters are proteins that span cellular membranes and that serve to carry neurotransmitters across these membranes and to transport them to specific locations. There are more than twenty types of neurotransmitter transporters.^[1] The transporters exist in the membranes of neurons and glia.

Vesicular transporters move neurotransmitters into synaptic vesicles, regulating the concentrations of substances within them.^[2] Vesicular transporters rely on a proton gradient created by the hydrolysis of adenosine triphosphate (ATP) in order to carry out their work: vesicle ATPase hydrolyzes ATP, causing protons to be pumped into the vesicle 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 use electrochemical gradients that exist across cell membranes to carry out their work. For example, some transporters use energy obtained by the cotransport of Na⁺ in order to move glutamate across membranes.

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.^[4]

Contents 1 Types 2 Clinical significance 3 See also 4 External links 5 References 6 External links

[edit] Types

Specific types of neurotransmitter transporters include the following:

• GABA transporters, including:
  • GABA transporter type 1 (GAT-1)
  • GABA transporter type 2 (GAT-2)
  • GABA transporter type 3 (GAT-3)
  • Betaine transporter (BGT-1)
  • Vesicular GABA transporter (VGAT)
• Glutamate transporters
• Glutamine transporters^[5]

• Glycine transporters, including:
  • Glycine transporter type 1 (GlyT-1)
  • Glycine transporter type 2 (GlyT-2)
• Monoamine transporters including:
  • The dopamine transporter, DAT.
  • The norepinephrine transporter, NET.
  • The serotonin transporter, SERT.
• Vesicular acetylcholine transporters^[6]

• Vesicular monoamine transporters

[edit] Clinical significance

Antidepressants act by inhibiting norepinephrine and serotonin reuptake transporters.^[1]

Cocaine exerts its effect by acting on the dopamine transporter.^[1]

The antiepileptic drug tiagabine prevents the uptake of GABA by acting on the GABA transporter GAT-1.^[1]

The expression of GABA transporter GAT-1 is decreased in the axonal cartridges of chandelier neurons in schizophrenia. ^[7]

[edit] See also

• K_i Database

[edit] External links

• Clearing Your Mind of Neurotransmitters: Functional Impact of Neurotransmitter Transporter Gene Variants - a videocast of the lecture by Randy Blakely, Ph.D., Vanderbilt University. Part of NIH Neuroscience Seminar series. 450 Mb file, .m4v format.
• The Blakely Lab - Laboratory exploring the molecular basis for neurotransmitter transporter structure, function and regulation.

[edit] References

1. ^ ^{a b c d} Iversen L. 2000. Neurotransmitter transporters: fruitful targets for CNS drug discovery Mol Psychiatry Volume 5, Issue 4, Pages 357-362. Accessed January 8, 2007.
2. ^ Johnson J, Tian N, Caywood MS, Reimer RJ, Edwards RH, and Copenhagen DR. 2003. Vesicular Neurotransmitter Transporter Expression in Developing Postnatal Rodent Retina: GABA and Glycine Precede Glutamate. The Journal of Neuroscience. Volume 23, Issue 2, Pages 518-529. Accessed January 8, 2007.
3. ^ Kandel ER, Schwartz JH, Jessell TM. 2000. Principles of Neural Science, 4th ed., Page 287. McGraw-Hill, New York ISBN 0-8385-7701-6
4. ^ Kandel ER, Schwartz JH, Jessell TM. 2000. Principles of Neural Science, 4th ed., Page 295. McGraw-Hill, New York ISBN 0-8385-7701-6
5. ^ Broer A, Albers A, Setiawan I, Edwards RH, Chaudhry FA, Lang F, Wagner CA, and Broer S. 2002. Regulation of the glutamine transporter SN1 by extracellular pH and intracellular sodium ions. Journal of Physiology. Volume 15; Issue 539 (Pt 1), Pages 3-14. Accessed January 8, 2007.
6. ^ Weihe E, Tao-Cheng JH, Schäfer MK, Erickson JD, and Eiden LE. 1996. Visualization of the vesicular acetylcholine transporter in cholinergic nerve terminals and its targeting to a specific population of small synaptic vesicles. Proceedings of the National Academy of Sciences of the U.S.A. Volume 93, Issue 8, Pages 3547–3552. Accessed January 8, 2007.
7. ^ Volk D, Austin M, Pierri J, Sampson A, Lewis D. (2001) GABA transporter-1 mRNA in the prefrontal cortex in schizophrenia: decreased expression in a subset of neurons. Am J Psychiatry. 158(2):256-65. PMID 11156808 free fulltext article

[edit] External links

• MeSH Neurotransmitter+Transporters