Neurotransmitter

Neurotransmitter

Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...

 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.

Vesicular transporters move neurotransmitters into synaptic vesicle

Synaptic vesicle

In a neuron, synaptic vesicles store various neurotransmitters that are released at the synapse. The release is regulated by a voltage-dependent calcium channel. Vesicles are essential for propagating nerve impulses between neurons and are constantly recreated by the cell...

s, regulating the concentrations of substances within them. Vesicular transporters rely on a proton gradient created by the hydrolysis

Hydrolysis

Hydrolysis is a chemical reaction during which molecules of water are split into hydrogen cations and hydroxide anions in the process of a chemical mechanism. It is the type of reaction that is used to break down certain polymers, especially those made by condensation polymerization...

 of adenosine triphosphate

Adenosine triphosphate

Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...

 (ATP) in order to carry out their work: vesicle ATPase hydrolyzes ATP, causing protons to be pumped into the Synaptic vesicle

Synaptic vesicle

In a neuron, synaptic vesicles store various neurotransmitters that are released at the synapse. The release is regulated by a voltage-dependent calcium channel. Vesicles are essential for propagating nerve impulses between neurons and are constantly recreated by the cell...

s and creating a proton gradient. Then the efflux of protons from the vesicle provides the energy to bring the neurotransmitter into the vesicle.

Neurotransmitter transporters frequently use electrochemical gradient

Electrochemical gradient

An electrochemical gradient is a spatial variation of both electrical potential and chemical concentration across a membrane; that is, a combination of the membrane potential and the pH gradient...

s that exist across cell membranes to carry out their work. For example, some transporters use energy obtained by the cotransport, or symport, of Na⁺

Sodium

Sodium is a chemical element with the symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals; its only stable isotope is 23Na. It is an abundant element that exists in numerous minerals, most commonly as sodium chloride...

 in order to move glutamate across membranes.

Normally, transporters in the synaptic

Synaptic

Synaptic may refer to:*Synapse, part of the nervous system*Synapsis, the pairing of two homologous chromosomes*Synaptic , a Linux graphical package management program for APT See also...

 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 receptor

Receptor (biochemistry)

In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...

s and exert their effect. This "nonvesicular release" of neurotransmitters is used by some cells, such as amacrine cell

Amacrine cell

Amacrine cells are interneurons in the retina. Amacrine cells are responsible for 70% of input to retinal ganglion cells. Bipolar cells, which are responsible for the other 30% of input to retinal ganglia, are regulated by amacrine cells.-Overview:...

s in the retina

Retina

The vertebrate retina is a light-sensitive tissue lining the inner surface of the eye. The optics of the eye create an image of the visual world on the retina, which serves much the same function as the film in a camera. Light striking the retina initiates a cascade of chemical and electrical...

, as a normal form of neurotransmitter release.

Types

Specific types of neurotransmitter transporters include the following:

• Glutamate/aspartate transporter
  Glutamate transporter
  Excitatory amino-acid transporters , formerly known as Glutamate transporters, belong to the family of neurotransmitter transporters. They serve to terminate the excitatory neurotransmitter signal by removal of glutamate from the neuronal synapse into Glia cells.In details, the EAATs are...
  
  s, including:
  • Excitatory amino acid transporter 1 (EAAT1)
  • Excitatory amino acid transporter 2
    SLC1A2
    Excitatory amino-acid transporter 2 also known as solute carrier family 1 member 2 is a protein that in humans is encoded by the SLC1A2 gene...
    
     (EAAT2)
  • Excitatory amino acid transporter 3
    SLC1A1
    Excitatory amino-acid transporter 3 is a protein that in humans is encoded by the SLC1A1 gene.-Further reading:...
    
     (EAAT3)
  • Excitatory amino acid transporter 4 (EAAT4)
  • Excitatory amino acid transporter 5 (EAAT5)
  • Vesicular glutamate transporter 1 (VGLUT1)
  • Vesicular glutamate transporter 2 (VGLUT2)
  • Vesicular glutamate transporter 3 (VGLUT3)

• GABA transporter
  GABA transporter
  GABA transporters are Neurotransmitter transporters including:** GABA transporter type 1 ** GABA transporter type 2 ** GABA transporter type 3 ** Betaine transporter ** Vesicular GABA transporter...
  
  s, including:
  • GABA transporter type 1 (GAT1)
  • GABA transporter type 2 (GAT2)
  • GABA transporter type 3 (GAT3)
  • Betaine transporter
    Betaine transporter
    Betaine / Carnitine / Choline Transporters are a family of prokaryotic transport proteins that are specific for compounds containing a quaternary nitrogen atom. The BCCT proteins contain 12 transmembrane regions and are energized by proton symport...
    
     (BGT1)
  • Vesicular GABA transporter (VGAT)

• Glycine transporters, including:
  • Glycine transporter type 1 (GlyT1)
  • Glycine transporter type 2 (GlyT2)

• Monoamine transporter
  Monoamine transporter
  Monoamine transporters are protein structures that function as integral plasma membrane transporters to regulate concentrations of extracellular monoamine neurotransmitters. Three major classes of MATs are responsible for the reuptake of their associated amine neurotransmitters...
  
  s, including:
  • Dopamine transporter
    Dopamine transporter
    The dopamine transporter is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synapse back into cytosol, from which other transporters sequester DA and NE into vesicles for later storage and release...
    
     (DAT)
  • Norepinephrine transporter
    Norepinephrine transporter
    The norepinephrine transporter , also known as solute carrier family 6 member 2 , is a protein that in humans is encoded by the SLC6A2 gene....
    
     (NET)
  • Serotonin transporter
    Serotonin transporter
    The serotonin transporter is a monoamine transporter protein.This protein is an integral membrane protein that transports the neurotransmitter serotonin from synaptic spaces into presynaptic neurons. This transport of serotonin by the SERT protein terminates the action of serotonin and recycles it...
    
     (SERT)
  • Vesicular monoamine transporter 1 (VMAT1)
  • Vesicular monoamine transporter 2 (VMAT2)

• Adenosine transporter
  Equilibrative nucleoside transporter
  The equilibrative nucleoside transporter family, also known as SLC29, is a group of plasmalemmal transport proteins which transport nucleoside substrates like adenosine into cells. There are four known ENTs, designated ENT1, ENT2, ENT3, and ENT4...
  
  s, including:
  • Equilibrative nucleoside transporter 1 (ENT1)
  • Equilibrative nucleoside transporter 2 (ENT2)
  • Equilibrative nucleoside transporter 3 (ENT3)
  • Equilibrative nucleoside transporter 4 (ENT4)

• Vesicular acetylcholine transporter
  Vesicular acetylcholine transporter
  The Vesicular acetylcholine transporter is a neurotransmitter transporter which is responsible for loading acetylcholine into secretory organelles in neurons making acetylcholine available for secretion.-Radiolabeled compounds:...
  
   (VAChT)

Note that there is no plasmalemmal acetylcholine

Acetylcholine

The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...

 transporter, as acetylcholine is terminated via rapid metabolism into choline

Choline

Choline is a water-soluble essential nutrient. It is usually grouped within the B-complex vitamins. Choline generally refers to the various quaternary ammonium salts containing the N,N,N-trimethylethanolammonium cation....

 by cholinesterase

Cholinesterase

In biochemistry, cholinesterase is a family of enzymes that catalyze the hydrolysis of the neurotransmitter acetylcholine into choline and acetic acid, a reaction necessary to allow a cholinergic neuron to return to its resting state after activation.-Types:...

 enzyme

Enzyme

Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

s, and choline is subsequently transported back into the cell and reconverted into acetylcholine.

Transporters associated with histamine

Histamine

Histamine is an organic nitrogen compound involved in local immune responses as well as regulating physiological function in the gut and acting as a neurotransmitter. Histamine triggers the inflammatory response. As part of an immune response to foreign pathogens, histamine is produced by...

 and the endocannabinoids have not yet been identified.

Clinical significance

Antidepressant

Antidepressant

An antidepressant is a psychiatric medication used to alleviate mood disorders, such as major depression and dysthymia and anxiety disorders such as social anxiety disorder. According to Gelder, Mayou &*Geddes people with a depressive illness will experience a therapeutic effect to their mood;...

s such as SSRIs

Selective serotonin reuptake inhibitor

Selective serotonin re-uptake inhibitors or serotonin-specific reuptake inhibitor are a class of compounds typically used as antidepressants in the treatment of depression, anxiety disorders, and some personality disorders. The efficacy of SSRIs is disputed...

, SNRIs

Serotonin-norepinephrine reuptake inhibitor

Serotonin–norepinephrine reuptake inhibitors are a class of antidepressant drugs used in the treatment of major depression and other mood disorders...

 and TCAs

Tricyclic antidepressant

Tricyclic antidepressants are heterocyclic chemical compounds used primarily as antidepressants. The TCAs were first discovered in the early 1950s and were subsequently introduced later in the decade; they are named after their chemical structure, which contains three rings of atoms...

 suppress the activity of serotonin and/or norepinephrine transporters, preventing the reuptake of targeted neurotransmitters from the synaptic cleft.

Psychostimulants like cocaine

Cocaine

Cocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. The name comes from "coca" in addition to the alkaloid suffix -ine, forming cocaine. It is a stimulant of the central nervous system, an appetite suppressant, and a topical anesthetic...

, amphetamine

Amphetamine

Amphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,...

s, and methylphenidate

Methylphenidate

Methylphenidate is a psychostimulant drug approved for treatment of attention-deficit hyperactivity disorder, postural orthostatic tachycardia syndrome and narcolepsy. It may also be prescribed for off-label use in treatment-resistant cases of lethargy, depression, neural insult and obesity...

 act by inhibiting and/or reversing the dopamine and norepinephrine transporters. Some dissociatives like phencyclidine

Phencyclidine

Phencyclidine , commonly initialized as PCP and known colloquially as angel dust, is a recreational dissociative drug...

 and ketamine

Ketamine

Ketamine is a drug used in human and veterinary medicine. Its hydrochloride salt is sold as Ketanest, Ketaset, and Ketalar. Pharmacologically, ketamine is classified as an NMDA receptor antagonist...

 are also dopamine transporter blockers.

Tiagabine

Tiagabine

Tiagabine -Indications:Tiagabine is approved by U.S. Food and Drug Administration as an adjunctive treatment for partial seizures in ages 12 and up. It may also be prescribed to treat anxiety disorders and neuropathic pain . For anxiety and neuropathic pain, tiagabine is used primarily to augment...

, a drug used as an anticonvulsant

Anticonvulsant

The anticonvulsants are a diverse group of pharmaceuticals used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of bipolar disorder, since many seem to act as mood stabilizers, and in the treatment of neuropathic pain. The goal of an...

, acts by inhibiting the GABA transporter 1.

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
  Vanderbilt University
  Vanderbilt University is a private research university located in Nashville, Tennessee, United States. Founded in 1873, the university is named for shipping and rail magnate "Commodore" Cornelius Vanderbilt, who provided Vanderbilt its initial $1 million endowment despite having never been to the...
  
  . Part of NIH
  National Institutes of Health
  The National Institutes of Health are an agency of the United States Department of Health and Human Services and are the primary agency of the United States government responsible for biomedical and health-related research. Its science and engineering counterpart is the National Science Foundation...
  
   Neuroscience Seminar series. 450 Mb file, .m4v
  MPEG-4 Part 14
  MPEG-4 Part 14 or MP4 is a multimedia container format standard specified as a part of MPEG-4. It is most commonly used to store digital video and digital audio streams, especially those defined by MPEG, but can also be used to store other data such as subtitles and still images...
  
  format.
• The Blakely Lab - Laboratory exploring the molecular basis for neurotransmitter transporter structure, function and regulation.