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This Article Full Text Full Text (PDF) All Versions of this Article: 557/3/747    most recent jphysiol.2004.062521v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Grewer, C. Articles by Grabsch, E. Search for Related Content PubMed PubMed Citation Articles by Grewer, C. Articles by Grabsch, E.

¹ University of Miami School of Medicine, 1600 NW 10th Avenue, Miami, FL 33136, USA² Max-Planck-Institut für Biophysik, Marie-Curie Str. 15, D-60439 Frankfurt, Germany

The neutral amino acid transporter ASCT2 catalyses uncoupled anion flux across the cell membrane in the presence of transported substrates, such as alanine. Here, we report that ASCT2 conducts anions already in the absence of transported substrates through a leak anion-conducting pathway. The properties of this leak anion conductance were studied by electrophysiological recording from ASCT2-expressing HEK293 cells. We found that the leak anion conductance was inhibited by the binding of the newly characterized inhibitors benzylserine and benzylcysteine to ASCT2. These inhibitors competitively prevent binding of transported substrates to ASCT2, suggesting that they bind to the ASCT2 binding site for neutral amino acid substrates. The leak anion conductance exhibits permeation properties that are similar to the substrate-activated anion conductance of ASCT2, preferring hydrophobic anions such as thiocyanate. Inhibition of the leak anion conductance by benzylserine requires the presence of extracellular, but not intracellular Na⁺. The apparent affinity of ASCT2 for extracellular Na⁺ was determined as 0.3 mM. Interestingly, a Na⁺-dependent leak anion conductance with similar properties was previously reported for the related excitatory amino acid transporters (EAATs), suggesting that this leak anion conductance is highly conserved within the EAAT protein family.

(Received 6 February 2004; accepted after revision 19 April 2004; first published online 23 April 2004)
Corresponding author C. Grewer: Department of Physiology and Biophysics, University of Miami School of Medicine, 1600 NW 10th Avenue, Miami, FL 33136, USA. Email: cgrewer{at}med.miami.edu

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