Inhibitors of GlyT1 and GlyT2 differentially modulate inhibitory transmission.
The chronic effects of glycine transporter 1 and 2 inhibitors (sarcosine and ALX-1393, respectively) on miniature inhibitory postsynaptic currents were studied in cultured spinal neurons. We found that sarcosine increased the frequency of overall miniature inhibitory postsynaptic currents without affecting the ratio of glycinergic, mixed and GABAergic miniature inhibitory postsynaptic currents, whereas ALX-1393 changed the ratio by increasing the proportions of GABAergic and mixed miniature inhibitory postsynaptic currents without affecting overall mIPSC frequency. We propose that inhibition of glycine transporter 1 by sarcosine increased overall mIPSC frequency via the activation of presynaptic glycine receptors, while inhibition of glycine transporter 2 by ALX-1393 changed the ratio of glycinergic, mixed and GABAergic miniature inhibitory postsynaptic currents by shifting the balance of inhibitory transmitters in vesicles towards gamma-aminobutyric acid.
Xu
Tai-Xiang
TX
Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China. tlxu@ion.ac.cn
Gong
Neng
N
Xu
Tian-Le
TL
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D026921:Amino Acid Transport Systems, Neutral / Q000037:antagonists & inhibitors*; D000818:Animals; D002478:Cells, Cultured; D004347:Drug Interactions; D004622:Embryo, Mammalian; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D050487:Glycine Plasma Membrane Transport Proteins; D008564:Membrane Potentials / Q000187:drug effects / Q000528:radiation effects; D009433:Neural Inhibition / Q000187:drug effects*; D018408:Patch-Clamp Techniques / Q000379:methods; D020671:Posterior Horn Cells / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012521:Sarcosine / Q000494:pharmacology*; D013116:Spinal Cord / Q000166:cytology; D009435:Synaptic Transmission / Q000187:drug effects*; D013779:Tetrodotoxin / Q000494:pharmacology
D026921:Amino Acid Transport Systems, Neutral; D018691:Excitatory Amino Acid Antagonists; D050487:Glycine Plasma Membrane Transport Proteins; C493269:Slc6a5 protein, rat; C493266:Slc6a9 protein, rat; D013779:Tetrodotoxin; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D012521:Sarcosine