Inactivation of the glycine transporter 1 gene discloses vital role of glial glycine uptake in glycinergic inhibition.
The glycine transporter subtype 1 (GlyT1) is widely expressed in astroglial cells throughout the mammalian central nervous system and has been implicated in the regulation of N-methyl-D-aspartate (NMDA) receptor activity. Newborn mice deficient in GlyT1 are anatomically normal but show severe motor and respiratory deficits and die during the first postnatal day. In brainstem slices from GlyT1-deficient mice, in vitro respiratory activity is strikingly reduced but normalized by the glycine receptor (GlyR) antagonist strychnine. Conversely, glycine or the GlyT1 inhibitor sarcosine suppress respiratory activity in slices from wild-type mice. Thus, during early postnatal life, GlyT1 is essential for regulating glycine concentrations at inhibitory GlyRs, and GlyT1 deletion generates symptoms found in human glycine encephalopathy.
Gomeza
Jesús
J
Department of Neurochemistry, Max-Planck-Institute for Brain Research, Deutschordenstrasse 46, 60528 Frankfurt, Germany.
Hülsmann
Swen
S
Ohno
Koji
K
Eulenburg
Volker
V
Szöke
Katalin
K
Richter
Diethelm
D
Betz
Heinrich
H
D026921:Amino Acid Transport Systems, Neutral / Q000172:deficiency* / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D004195:Disease Models, Animal; D005804:Genes, Lethal / Q000235:genetics; D005998:Glycine / Q000378:metabolism* / Q000493:pharmacokinetics; D050487:Glycine Plasma Membrane Transport Proteins; D006720:Homozygote; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009433:Neural Inhibition / Q000235:genetics*; D009457:Neuroglia / Q000378:metabolism*; D010641:Phenotype; D012119:Respiration / Q000187:drug effects; D012521:Sarcosine / Q000494:pharmacology; D013331:Strychnine / Q000494:pharmacology; D009435:Synaptic Transmission / Q000235:genetics
D026921:Amino Acid Transport Systems, Neutral; D050487:Glycine Plasma Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493267:Slc6a9 protein, mouse; D013331:Strychnine; D005998:Glycine; D012521:Sarcosine