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Cited by 993

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

Functional comparisons of three glutamate transporter subtypes cloned from human motor cortex

Open access
Arriza, JL, Fairman, WA, Wadiche, JI, Murdoch, GH, Kavanaugh, MP, Amara, SG·1994·The Journal of Neuroscience
DOI 10.1523/jneurosci.14-09-05559.1994
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Abstract

Reuptake plays an important role in regulating synaptic and extracellular concentrations of glutamate. Three glutamate transporters expressed in human motor cortex, termed EAAT1, EAAT2, and EAAT3 (for excitatory amino acid transporter), have been characterized by their molecular cloning and functional expression. Each EAAT subtype mRNA was found in all human brain regions analyzed. The most prominent regional variation in message content was in cerebellum where EAAT1 expression predominated. EAAT1 and EAAT3 mRNAs were also expressed in various non- nervous tissues, whereas expression of EAAT2 was largely restricted to brain. The kinetic parameters and pharmacological characteristics of transport mediated by each EAAT subtype were determined in transfected mammalian cells by radio-label uptake and in microinjected oocytes by voltage-clamp measurements. The affinities of the EAAT subtypes for L- glutamate were similar, with Km determinations varying from 48 to 97 microM in the mammalian cell assay and from 18 to 28 microM in oocytes. Glutamate uptake inhibitors were used to compare the pharmacologies of the EAAT subtypes. The EAAT2 subtype was distinguishable from the EAAT1/EAAT3 subtypes by the potency of several inhibitors, but most notably by sensitivity to kainic acid (KA) and dihydrokainic acid (DHK). KA and DHK potently inhibited EAAT2 transport, but did not significantly affect transport by EAAT1/EAAT3. Using voltage-clamp measurements, most inhibitors were found to be substrates that elicited transport currents. In contrast, KA and DHK did not evoke currents and they were found to block EAAT2-mediated transport competitively. This selective interaction with the EAAT2 subtype could be a significant factor in KA neurotoxicity. These studies provide a foundation for understanding the role of glutamate transporters in human excitatory neurotransmission and in neuropathology.

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Metadata

Authors
Arriza, J., Fairman, W., Wadiche, J., Murdoch, G., Kavanaugh, M., & Amara, S.
Venue
The Journal of Neuroscience
Publisher
Society for Neuroscience
Published
1994-09-01
Volume
14
Issue
9
Pages
5559-5569
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
DOI
10.1523/jneurosci.14-09-05559.1994
OpenAlex
W2157853053
Cited by
993
References
1
FWCI
12.60
Type
journal article
Language
en
Open access
hybrid

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