Control of NMDA Receptor Activation by a Glycine Transporter Co-Expressed inXenopusOocytes
| Autor: | Claude Bergman, Stéphane Supplisson |
|---|---|
| Přispěvatelé: | Supplisson, Stéphane, Neurobiologie cellulaire et moléculaire (NCM), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Paris (ENS Paris) |
| Rok vydání: | 1997 |
| Předmět: |
Patch-Clamp Techniques
[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology Xenopus D-serine Glycine Plasma Membrane Transport Proteins Membrane Potentials Glycine transporter Xenopus laevis 0302 clinical medicine MESH: Animals MESH: Amino Acid Transport Systems Neutral 0303 health sciences MESH: Kinetics biology musculoskeletal neural and ocular physiology General Neuroscience MESH: Glycine Plasma Membrane Transport Proteins Brain MESH: Glutamic Acid Articles MESH: Glycine Recombinant Proteins Spinal Cord Biochemistry MESH: Receptors N-Methyl NMDA receptor Female GlyT1 Glycine Glutamic Acid MESH: Carrier Proteins In Vitro Techniques Receptors N-Methyl-D-Aspartate MESH: Oocytes MESH: Brain 03 medical and health sciences MESH: Patch-Clamp Techniques MESH: Membrane Potentials Animals Humans 030304 developmental biology MESH: Humans Cell Membrane [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology Biological membrane biology.organism_classification Kinetics Amino Acid Transport Systems Neutral NMDA nervous system Glycine transporter 1 Oocytes biology.protein Biophysics Carrier Proteins Cotransporter MESH: Female 030217 neurology & neurosurgery MESH: Cell Membrane |
| Zdroj: | Journal of Neuroscience Journal of Neuroscience, 1997, 17 (12), pp.4580-90 Journal of Neuroscience, Society for Neuroscience, 1997, 17 (12), pp.4580-90 |
| ISSN: | 1529-2401 0270-6474 |
| Popis: | We present evidence that membrane transporters can control the membrane receptor’s agonist concentration in restricted extracellular spaces of a biological model. The model is constructed by co-expressing glycine/Na/Cl cotransporters (GLYT1b) and NMDA receptors (NMDARs) (composed of the subunits NR1 and NR2A or NR2B) inXenopusoocytes. We use the high-affinity glycine site of the NMDARs as a sensor of the actual juxtamembrane glycine concentration. We show that glycine uptake by GLYT1b dramatically reduces NMDAR currents by reducing the glycine concentration in extracellular spaces in which diffusion is restricted. This effect appears only in oocytes in which GLYT1b and NMDAR are co-expressed. It is Na+- and voltage-dependent, and is abolished when Na+is replaced by Li+and when glycine is replaced byd-serine (a coagonist of the NMDAR that is not transported by GLYT1b). These results demonstrate the ability of the GLYT transporter to reduce glycine concentration at the level of NMDARs in restricted diffusion spaces. This observation could account for a prevalent role of membrane transporters in the modulation of synapse transmission in the CNS. From a more general point of view, our results draw attention to possible significant discrepancies between local concentrations at the level of substrate targets in biological membranes and their concentration in the bulk solution when membrane transporters are present. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|