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Neurotransmitter transporter

{{Short description|Class of membrane transport proteins}}

Neurotransmitter transporters are a class of membrane transport proteins that span the cellular membranes of neurons. Their primary function is to carry neurotransmitters across these membranes and to direct their further transport to specific intracellular locations. There are more than twenty types of neurotransmitter transporters.{{cite journal |author=Iversen L |title=Neurotransmitter transporters: fruitful targets for CNS drug discovery |journal=Mol. Psychiatry |volume=5 |issue=4 |pages=357–62 |date=July 2000 |pmid=10889545 |url=http://www.biopsychiatry.com/transporters.htm |doi=10.1038/sj.mp.4000728|doi-access= |url-access=subscription }}

Vesicular transporters move neurotransmitters into synaptic vesicles, regulating the concentrations of substances within them.{{cite journal |vauthors=Johnson J, Tian N, Caywood MS, Reimer RJ, Edwards RH, Copenhagen DR |title=Vesicular neurotransmitter transporter expression in developing postnatal rodent retina: GABA and glycine precede glutamate |journal=J. Neurosci. |volume=23 |issue=2 |pages=518–29 |date=January 2003 |pmid=12533612 |doi=10.1523/JNEUROSCI.23-02-00518.2003 |doi-access=free |pmc=6741860 }} Vesicular transporters rely on a proton gradient created by the hydrolysis of adenosine triphosphate (ATP) in order to carry out their work: v-ATPase hydrolyzes ATP, causing protons to be pumped into the synaptic vesicles and creating a proton gradient. Then the efflux of protons from the vesicle provides the energy to bring the neurotransmitter into the vesicle.{{cite book |author=Kandel ER, Schwartz JH, Jessell TM |title=Principles of neural science |publisher=McGraw-Hill |location=New York |year=2000 |page=[https://archive.org/details/isbn_9780838577011/page/287 287] |isbn=0-8385-7701-6 |edition=4th|title-link=Principles of neural science }}

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.{{cite journal |last1=Amara |first1=Susan G. |last2=Kuhar |first2=Michael J. |year=1993 |title=Neurotransmitter Transporters:Recent Progress |journal=Annual Review of Neuroscience |volume=16 |issue=1 |pages=73–93 |doi=10.1146/annurev.ne.16.030193.000445|pmid=8096377 |url=https://zenodo.org/record/1235039 }}

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.{{cite book |author=Kandel ER, Schwartz JH, Jessell TM |title=Principles of neural science |publisher=McGraw-Hill |location=New York |year=2000 |page=[https://archive.org/details/isbn_9780838577011/page/295 295] |isbn=0-8385-7701-6 |edition=4th|title-link=Principles of neural science }}

Types

{{Synapse map}}

Specific types of neurotransmitter transporters include the following:

Note that there is no plasmalemmal acetylcholine transporter, as acetylcholine is terminated via rapid metabolism into choline by cholinesterase enzymes, and choline is subsequently transported back into the cell and reconverted into acetylcholine.

Transporters associated with histamine and the endocannabinoids have not yet been identified.

Clinical significance

A variety of neurotransmitter reuptake transporters are pharmacotherapeutic targets for modulating the synaptic neurotransmitter concentration, and therefore neurotransmission.

File:Neurotransmitter transporters inhibitors.png

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.{{cite journal |vauthors=Varoqui H, Erickson JD |title=Vesicular neurotransmitter transporters. Potential sites for the regulation of synaptic function |journal=Molecular Neurobiology |volume=15 |issue=2 |pages=165–91 | date=October 1997 |pmid=9396009 |doi=10.1007/BF02740633|s2cid=26111849 }}

  • Vesamicol, for example, is an inhibitor of the vesicular acetylcholine transporter. It prevents the loading of ACh into the presynaptic vesicles, causing a fall in the amount that is released in response to a neuronal action potential. It is not used clinically, but provides a useful tool for research into the behaviour of neurotransmitter vesicles.{{cite journal |vauthors=Prior C, Marshall IG, Parsons SM |title=The pharmacology of vesamicol: an inhibitor of the vesicular acetylcholine transporter |journal=General Pharmacology |volume=23 |issue=6 |pages=1017–22 | date=November 1992 |pmid=1487110 |doi=10.1016/0306-3623(92)90280-w}}

References

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External links

{{Commonscat|Neurotransmitter transporters}}

  • {{MeshName|Neurotransmitter+Transporters}}
  • [https://web.archive.org/web/20060929042009/http://videocast.nih.gov/PastEventDetail.asp?13354 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.
  • [https://web.archive.org/web/20070306012319/http://web.mac.com/rdblakely/iWeb/BlakelyLab/Home.html The Blakely Lab] - Laboratory exploring the molecular basis for neurotransmitter transporter structure, function and regulation.

{{Neurotransmitters}}

{{Neuromodulation}}

{{Membrane transport proteins}}

{{Neurotransmitter transporters}}

{{DEFAULTSORT:Neurotransmitter Transporter}}

Category:Integral membrane proteins