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]

[edit] Types

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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

[edit] External links

• MeSH Neurotransmitter+Transporters