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Biophys. J. BioFAST: First Published June 10, 2005. doi:10.1529/biophysj.105.061572
© 2005 by the Biophysical Society.


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CHANNELS, RECEPTORS, AND ELECTRICAL SIGNALING

DYNAMICS OF FORWARD AND REVERSE TRANSPORT BY THE GLIAL GLYCINE TRANSPORTER, GLYT1B

Karin R. Aubrey 1*, Robert J. Vandenberg 2 and John D. Clements 3

1 University of Sydney; Ecole Normale Supérieure
2 University of Sydney
3 Australian National University

* To whom correspondence should be addressed. E-mail: aubrey{at}biologie.ens.fr.

Submitted on February 18, 2005
Revised on April 25, 2005
Accepted on 18 May 2005


   Abstract
Glycine is a co-agonist at the N-methyl-D-aspartate receptor. Changes in extracellular glycine concentration may modulate N-methyl-D-aspartate receptor function and excitatory synaptic transmission. The GLYT1 glycine transporter is present in glia surrounding excitatory synapses, and plays a key role in regulating extracellular glycine concentration. We investigated the kinetic and other biophysical properties of GLYT1b, stably expressed in CHO cells, using whole-cell patch clamp techniques. Application of glycine produced an inward current, which decayed within a few seconds to a steady-state level. When glycine was removed a transient outward current was observed, consistent with reverse transport of accumulated glycine. The outward current was enhanced by elevating intracellular or lowering extracellular [Na+], and was modulated by changes in extracellular [glycine] and time of glycine application. We developed a model of GLYT1b function, which accurately describes the time course of the transporter current under a range of experimental conditions. The model predicts that glial uptake of glycine will decay toward zero during a sustained period of elevated glycine concentration. This property of GLYT1b may permit spillover from glycinergic terminals to nearby excitatory terminals during a prolonged burst of inhibitory activity, and reverse transport may extend the period of elevated glycine concentration beyond the end of the inhibitory burst.

Key Words: CNS, amino acid transporters, glycine release, kinetic modeling, whole cell electrophysiology




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Copyright © 2005 by the Biophysical Society.