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The Journal of Neuroscience, January 1, 2002, 22(1):62-72
Glutamine Uptake by Neurons: Interaction of Protons with System A
Transporters
Farrukh A.
Chaudhry1, 4,
Dietmar
Schmitz2, 4,
Richard
J.
Reimer1, 4,
Peter
Larsson5,
Andrew T.
Gray3,
Roger
Nicoll2, 4,
Michael
Kavanaugh5, and
Robert H.
Edwards1, 4
Departments of 1 Neurology, 2 Pharmacology,
3 Anesthesia, and 4 Physiology, Graduate
Programs in Neuroscience, Cell Biology and Biomedical Sciences,
University of California San Francisco School of Medicine, San
Francisco, California 94143-0435, and 5 Vollum Institute,
Oregon Health Sciences University, Portland, Oregon 97201
Astrocytes provide the glutamine required by neurons to synthesize
glutamate and GABA. However, the mechanisms involved in glutamine
transfer from glia to neurons have remained poorly understood. Recent
work has implicated the System N transporter SN1 in the efflux of
glutamine from astrocytes and the very closely related System A
transporters SA1 and SA2 in glutamine uptake by neurons. To understand
how these closely related proteins mediate flux in different
directions, we have examined their ionic coupling. In contrast to the
electroneutral exchange of H+ for
Na+ and neutral amino acid catalyzed by SN1, we now
show that SA1 and SA2 do not couple H+ movement to
amino acid flux. As a result, SA1 and SA2 are electrogenic and do not
mediate flux reversal as readily as SN1. Differences between System N
and A transporters in coupling to H+ thus contribute
to the delivery of glutamine from glia to neurons. Nonetheless,
although they are not transported, H+ inhibit SA1
and SA2 by competing with Na+.
Key words:
glutamine-glutamate cycle; system A; system N; glutamine; synaptic transmission; H+ coupling
Copyright © 2002 Society for Neuroscience 0270-6474/02/22162-11$05.00/0
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