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The system N transporter SN2 doubles as a transmitter precursor furnisher and a potential regulator of NMDA receptors
Author(s) -
Hamdani El Hassan,
Gudbrandsen Marius,
Bjørkmo Mona,
Chaudhry Farrukh Abbas
Publication year - 2012
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.22386
Subject(s) - nmda receptor , sn2 reaction , glutamate receptor , biology , glycine , glycine receptor , glutamine , regulator , transporter , neuroscience , microbiology and biotechnology , biophysics , receptor , biochemistry , chemistry , amino acid , stereochemistry , gene
Activation of NMDA receptor requires two co‐agonists, glutamate and glycine. Despite its intrinsic role in brain functions molecular mechanisms involved in glutamate replenishment and identification of the origin of glycine have eluded characterization. We have performed direct measurements of glycine flux by SN2 (Slc38a5; also known as SNAT5), executed extensive electrophysiological characterization as well as implemented ratiometric analyses to show that SN2 transport resembles SN1 in mechanism but differ in functional implications. We report that rat SN2 mediates electroneutral and bidirectional transport of glutamine and glycine at perisynaptic astroglial membranes. Sophisticated coupled and uncoupled movements of H + differentially associate with glutamine and glycine transport by SN2 and regulate pH i and the release mode of the transporter. Consequently, SN2 doubles as a transmitter precursor furnisher and a potential regulator of NMDA receptors. © 2012 Wiley Periodicals, Inc.