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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. Chaudhry^{1, 4}, Dietmar Schmitz^{2, 4}, Richard J. Reimer^{1, 4}, Peter Larsson⁵, Andrew T. Gray³, Roger Nicoll^{2, 4}, Michael Kavanaugh⁵, and Robert H. Edwards^{1, 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

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Copyright © 2002 Society for Neuroscience  0270-6474/02/22162-11$05.00/0

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