Water and urea permeation pathways of the human excitatory amino acid transporter EAAT1

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dc.contributor.authorVandenberg, R.
dc.contributor.authorHandford, C.
dc.contributor.authorCampbell, E.
dc.contributor.authorRyan, R.
dc.contributor.authorYool, A.
dc.date.issued2011
dc.description.abstractGlutamate transport is coupled to the co-transport of 3 Na(+) and 1 H(+) followed by the counter-transport of 1 K(+). In addition, glutamate and Na(+) binding to glutamate transporters generates an uncoupled anion conductance. The human glial glutamate transporter EAAT1 (excitatory amino acid transporter 1) also allows significant passive and active water transport, which suggests that water permeation through glutamate transporters may play an important role in glial cell homoeostasis. Urea also permeates EAAT1 and has been used to characterize the permeation properties of the transporter. We have previously identified a series of mutations that differentially affect either the glutamate transport process or the substrate-activated channel function of EAAT1. The water and urea permeation properties of wild-type EAAT1 and two mutant transporters were measured to identify which permeation pathway facilitates the movement of these molecules. We demonstrate that there is a significant rate of L-glutamate-stimulated passive and active water transport. Both the passive and active L-glutamate-stimulated water transport is most closely associated with the glutamate transport process. In contrast, L-glutamate-stimulated [(14)C]urea permeation is associated with the anion channel of the transporter. However, there is also likely to be a transporter-specific, but glutamate independent, flux of water via the anion channel.
dc.description.statementofresponsibilityRobert J. Vandenberg, Cheryl A. Handford, Ewan M. Campbell, Renae M. Ryan and Andrea J. Yool
dc.identifier.citationBiochemical Journal, 2011; 439(2):333-340
dc.identifier.doi10.1042/BJ20110905
dc.identifier.issn0264-6021
dc.identifier.issn1470-8728
dc.identifier.orcidYool, A. [0000-0003-1283-585X]
dc.identifier.urihttp://hdl.handle.net/2440/68776
dc.language.isoen
dc.publisherPortland Press
dc.relation.grantNHMRC
dc.relation.granthttp://purl.org/au-research/grants/arc/DP1092729
dc.relation.granthttp://purl.org/au-research/grants/arc/DP1092729
dc.rights© The Authors Journal compilation © 2011 Biochemical Society
dc.source.urihttps://doi.org/10.1042/bj20110905
dc.subjectanion channel
dc.subjectglutamate transport
dc.subjecturea
dc.subjectwater transport.
dc.titleWater and urea permeation pathways of the human excitatory amino acid transporter EAAT1
dc.typeJournal article
pubs.publication-statusPublished

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