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Excitatory Amino Acid Transporters (EAAT), formerly known as Glutamate transporters, belong to the family of neurotransmitter transporters. They serve to terminate the excitatory neurotransmitter signal by removal (uptake) of glutamate from the neuronal synapse into Glia cells.

In details, the EAATs are membrane-bound pumps that resemble ion channels.[1] These transporters play the important role of regulating concentrations of glutamate in the extracellular space, keeping it at low levels.[2] After glutamate is released as the result of an action potential, glutamate transporters quickly remove it from the extracellular space to keep its levels low, thereby terminating the synaptic transmission.[1][3]

Without the activity of glutamate transporters, glutamate would build up and kill cells in a process called excitotoxicity, in which excessive amounts of glutamate acts as a toxin to neurons by triggering a number of biochemical cascades. The activity of glutamate transporters also allows glutamate to be recycled for repeated release.[4]

Glutamate transporters are also present in many other tissues such as bone and testes.



There are two classes of glutamate transporters, those that are dependent on an electrochemical gradient of sodium ions (the EAATs) and those that are not (VGluTs).[5] Some sodium independent transporters such as the cystine-glutamate antiporter (xCT) are localised to plasma membrane of cells whilst others the are called vesicular transporters. Na+-dependent transporters are actually also dependent on K+ concentrations, and so are also known as 'sodium and potassium coupled glutamate transporters' or, in humans, 'excitatory amino acid transporters' (EAATs).[6] Some Na+-dependent transporters have also been called 'high-affinity transporters', though their glutamate affinity actually varies widely.[6]

mitochondria also possess mechanisms for taking up glutamate that are quite distinct from membrane glutamate transporters.[6]



In humans (as well as in rodents), five subtypes have been identified and named EAAT1-5 (SLC1A3, SLC1A2, SLC1A1, SLC1A6, SLC1A7). Subtypes EAAT1-3 are found in membranes of glial cells (astrocytes, microglia, and oligodendrocytes) as well as in endothelial cells, whereas EAAT4 is located on neurons.[5]. Finally, EAAT5 is only found in the retina where it is principally localised to photoreceptors and bipolar neurons in the retina.[7]. In rodents, the orthologs for EAAT1-3 are named GLAST, GLT1, and EAAC1, respectively[3], whereas the acronyms EAAT4 and EAAT5 are conserved.

When glutamate is taken up into Glia cells by the EAATs, it is not reused directly but converted to glutamine and stored in vesicles. Subsequently these vesicles are released from Glia cells and glutamine transported back into the presynaptic neuron, converted back into glutamate, and store into vesicles by action of the VGLUTs.[8][3] This process is named the glutamate-glutamine cycle.

The Glia transporters - in particularly the various splice variants of GLT-1 (EAAT2) - play the largest role (90%) in regulating extracellular glutamate concentration.[9]

protein gene tissue distribution
EAAT1 SLC1A3 glial and endothelial cells
EAAT2 SLC1A2 glial and endothelial cells
EAAT3 SLC1A1 glial and endothelial cells
EAAT4 SLC1A6 neurons
EAAT5 SLC1A7 retina
VGLUT1 SLC17A7 neurons
VGLUT2 SLC17A6 neurons
VGLUT3 SLC17A8 neurons


Four types of vesicular glutamate transporters are known, VGLUTs 1–3 [10](SLC17A7, SLC17A6, SLC17A8)[3] and the novel glutamate/aspartate transporter sialin [11]. These transporters pack the neurotransmitter into synaptic vesicles so that they can be released into the synapse. VGLUTs are dependent on the proton gradient that exists in the secretory system (vesicles being more acid than the cytosol). VGLUTs have only between one hundredth and one thousandth the affinity for glutamate that EAATs have.[3] Also unlike EAATs, they do not appear to transport aspartate.


Overactivity of glutamate transporters may result in inadequate synaptic glutamate and may be involved in schizophrenia and other mental illnesses.[1]

During injury processes such as ischemia and traumatic brain injury, the action of glutamate transporters may fail, leading to toxic buildup of glutamate. In fact, their activity may also actually be reversed due to inadequate amounts of adenosine triphosphate to power ATPase pumps, resulting in the loss of the electrochemical ion gradient. Since the direction of glutamate transport depends on the ion gradient, these transporters release glutamate instead of removing it, which results in neurotoxicity due to overactivation of glutamate receptors.[12]

Loss of the Na+-dependent glutamate transporter EAAT2 is suspected to be associated with neurodegenerative diseases such as Alzheimer's disease, Huntington's disease, and ALS–parkinsonism dementia complex.[13] Also, degeneration of motor neurons in the disease amyotrophic lateral sclerosis has been linked to loss of EAAT2 from patients' brains and spinal cords.[13]

See also


  1. ^ a b c Ganel R, Rothstein JD (1999). "Chapter 15, Glutamate transporter dysfunction and neuronal death". in Monyer, Hannah; Gabriel A. Adelmann; Jonas, Peter. Ionotropic glutamate receptors in the CNS. Berlin: Springer. pp. 472–493. ISBN 3-540-66120-4.  
  2. ^ Han BC, Koh SB, Lee EY, Seong YH (2004). "Regional difference of glutamate-induced swelling in cultured rat brain astrocytes". Life Sci. 76 (5): 573–83. doi:10.1016/j.lfs.2004.07.016. PMID 15556169.  
  3. ^ a b c d e Shigeri Y, Seal RP, Shimamoto K (2004). "Molecular pharmacology of glutamate transporters, EAATs and VGLUTs". Brain Res. Brain Res. Rev. 45 (3): 250–65. doi:10.1016/j.brainresrev.2004.04.004. PMID 15210307.  
  4. ^ Zou JY, Crews FT (2005). "TNF alpha potentiates glutamate neurotoxicity by inhibiting glutamate uptake in organotypic brain slice cultures: neuroprotection by NF kappa B inhibition". Brain Res. 1034 (1-2): 11–24. doi:10.1016/j.brainres.2004.11.014. PMID 15713255.  
  5. ^ a b Anderson CM, Swanson RA (2000). "Astrocyte glutamate transport: review of properties, regulation, and physiological functions". Glia 32 (1): 1–14. doi:10.1002/1098-1136(200010)32:1. PMID 10975906.  
  6. ^ a b c Danbolt NC (2001). "Glutamate uptake". Prog. Neurobiol. 65 (1): 1–105. doi:10.1016/S0301-0082(00)00067-8. PMID 11369436.  
  7. ^ Pow DV, Barnett NL (2000). "Developmental expression of excitatory amino acid transporter 5: a photoreceptor and bipolar cell glutamate transporter in rat retina". Neurosci. Lett. 280 (1): 21–4. doi:10.1016/S0304-3940(99)00988-X. PMID 10696802.  
  8. ^ Pow DV, Robinson SR (1994). "Glutamate in some retinal neurons is derived solely from glia". Neuroscience 60 (2): 355–66. doi:10.1016/0306-4522(94)90249-6. PMID 7915410.  
  9. ^ Shachnai L, Shimamoto K, Kanner BI (2005). "Sulfhydryl modification of cysteine mutants of a neuronal glutamate transporter reveals an inverse relationship between sodium dependent conformational changes and the glutamate-gated anion conductance". Neuropharmacology 49 (6): 862–71. doi:10.1016/j.neuropharm.2005.07.005. PMID 16137722.  
  10. ^ Naito S and Ueda T (1983). "Adenosine triphosphate-dependent uptake of glutamate into protein I- associated synaptic vesicles". J. of Biological Chemistry 258: 696-699.  
  11. ^ Miyaji T, Echigo N, Hiasa M, Senoh S, Omote H, Moriyama Y. Identification of a vesicular aspartate transporter. Proc Natl Acad Sci U S A. 2008;105:11720-4.PMID: 18695252
  12. ^ Kim AH, Kerchner GA, Choi DW (2002). "Chapter 1, Blocking Excitotoxicity". in Marcoux, Frank W.. CNS neuroprotection. Berlin: Springer. pp. 3–36. ISBN 3-540-42412-1.  
  13. ^ a b Yi JH, Hazell AS (2006). "Excitotoxic mechanisms and the role of astrocytic glutamate transporters in traumatic brain injury". Neurochem. Int. 48 (5): 394–403. doi:10.1016/j.neuint.2005.12.001. PMID 16473439.  

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