Role of taurine uptake on the induction of long-term synaptic potentiation.
Taurine application in the CA1 area of rat hippocampal slices induces a long-lasting potentiation of excitatory synaptic transmission that has some mechanistic similitude with the late phase of long-term potentiation (L-LTP). Previous indirect evidence such as temperature and sodium dependence indicated that taurine uptake is one of the primary steps leading to the taurine-induced synaptic potentiation. We show that taurine-induced potentiation is not related to the intracellular accumulation of taurine and is not impaired by 2-guanidinoethanesulphonic acid, a taurine transport inhibitor that is a substrate of taurine transporter. We have found that taurine uptake in hippocampal synaptosomes was inhibited by SKF 89976A, a GABA uptake blocker that is not transportable by GABA transporters. SKF 89976A prevents the induction of synaptic potentiation by taurine application. This effect is neither mimicked by nipecotic acid, a broad inhibitor of GABA transporters that does not affect taurine uptake, nor by NO-711, a specific and potent inhibitor of GABA transporter GAT-1. In addition, L-LTP induced by trains of high-frequency stimulation is also inhibited by SKF 89976A, and taurine, at a concentration that does not change basal synaptic transmission, overcomes such inhibition. We conclude that taurine induces synaptic potentiation through the activation of a system transporting taurine and that taurine uptake is required for the induction of synaptic plasticity phenomena such as L-LTP.
del Olmo
Nuria
N
Departamento de Psicobiología, Facultad Psicología, UNED, Madrid, Spain.
Suárez
Luz M
LM
Orensanz
Luis M
LM
Suárez
Francisco
F
Bustamante
Julián
J
Duarte
José M
JM
Martín del Río
Rafael
R
Solís
José M
JM
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D002352:Carrier Proteins / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D042541:Intracellular Space / Q000187:drug effects; D017774:Long-Term Potentiation / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors; D026901:Membrane Transport Proteins; D009557:Nipecotic Acids / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D013654:Taurine / Q000378:metabolism*; D000099247:Taurine Transporters
D015763:2-Amino-5-phosphonovalerate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D002352:Carrier Proteins; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D006146:Guanidines; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009557:Nipecotic Acids; D013654:Taurine; D000099247:Taurine Transporters; C030278:nipecotic acid; C028748:2-guanidinoethylphosphonic acid