Glutamate uptake from the synaptic cleft does not shape the decay of the non-NMDA component of the synaptic current

To study the role of glutamate uptake at central glutamatergic synapses, we used the uptake blocker L-transpyrrolidine-2,4-dicarboxylate (PDC). The effects of PDC on the glutamate uptake current in salamander retinal glia indicated that PDC competes with glutamate for transport on the uptake carrier and that 300 microM PDC should significantly reduce the uptake of glutamate during the synaptic current. In isolated rat hippocampal neurons, 300 microM PDC did not affect non-N-methyl-D-aspartate (NMDA) receptor currents, but reduced NMDA receptor currents by 30%. In hippocampal and cerebellar slices, whereas 300 microM PDC reduced the NMDA component of excitatory synaptic currents by 50%, it reduced the non-NMDA component only slightly with no change in its decay time constant. Thus, the decay rate of the non-NMDA component is not set by the rate of glutamate uptake from the synaptic cleft into the presynaptic terminal.

[1]  B. Sakmann,et al.  Action of brief pulses of glutamate on AMPA/kainate receptors in patches from different neurones of rat hippocampal slices. , 1992, The Journal of physiology.

[2]  G. Westbrook,et al.  The time course of glutamate in the synaptic cleft. , 1992, Science.

[3]  R. Nicoll,et al.  Local and diffuse synaptic actions of GABA in the hippocampus , 1993, Neuron.

[4]  L. Kerkérian,et al.  Modulatory Effect of Dopamine on High‐Affinity Glutamate Uptake in the Rat Striatum , 1987, Journal of neurochemistry.

[5]  David Attwell,et al.  The glial cell glutamate uptake carrier countertransports pH-changing anions , 1992, Nature.

[6]  P. Ascher,et al.  Activation and desensitization of N‐methyl‐D‐aspartate receptors in nucleated outside‐out patches from mouse neurones. , 1992, The Journal of physiology.

[7]  J. Bockaert,et al.  NMDA receptors activate the arachidonic acid cascade system in striatal neurons , 1988, Nature.

[8]  P. Chan,et al.  Reductions of Γ‐Aminobutyric Acid and Glutamate Uptake and (Na++ K+)‐ATPase Activity in Brain Slices and Synaptosomes by Arachidonic Acid , 1983, Journal of neurochemistry.

[9]  Shaul Hestrin,et al.  Activation and desensitization of glutamate-activated channels mediating fast excitatory synaptic currents in the visual cortex , 1992, Neuron.

[10]  R. Sapolsky,et al.  Glucocorticoids Inhibit Glucose Transport and Glutamate Uptake in Hippocampal Astrocytes: Implications for Glucocorticoid Neurotoxicity , 1991, Journal of neurochemistry.

[11]  R. Lester,et al.  Synaptic activation of N‐methyl‐D‐aspartate receptors in the Schaffer collateral‐commissural pathway of rat hippocampus. , 1988, The Journal of physiology.

[12]  S. Schuldiner,et al.  Mechanism of Transport and Storage of Neurotransmitter , 1987 .

[13]  D. Attwell,et al.  Glutamate uptake in mammalian retinal glia is voltage- and potassium-dependent , 1990, Brain Research.

[14]  D. Attwell,et al.  Electrogenic uptake of glutamate and aspartate into glial cells isolated from the salamander (Ambystoma) retina. , 1991, The Journal of physiology.

[15]  J. Bockaert,et al.  Arachidonic acid released from striatal neurons by joint stimulation of ionotropic and metabotropic quisqualate receptors , 1990, Nature.

[16]  M. Casado,et al.  Activation of High‐Affinity Uptake of Glutamate by Phorbol Esters in Primary Glial Cell Cultures , 1991, Journal of neurochemistry.

[17]  R. Nicoll,et al.  Mechanisms generating the time course of dual component excitatory synaptic currents recorded in hippocampal slices , 1990, Neuron.

[18]  D. Attwell,et al.  The potassium-dependence of excitatory amino acid transport: resolution of a paradox , 1991, Brain Research.

[19]  M. Hediger,et al.  Primary structure and functional characterization of a high-affinity glutamate transporter , 1992, Nature.

[20]  J. Coyle,et al.  Heterogeneity of sodium‐dependent excitatory amino uptake mechanisms in rat brain , 1986, Journal of neuroscience research.

[21]  R. Dingledine,et al.  Regional variation of extracellular space in the hippocampus. , 1990, Science.

[22]  J. Clements,et al.  Presynaptic glutamate receptors depress excitatory monosynaptic transmission between mouse hippocampal neurones. , 1990, The Journal of physiology.

[23]  G. Westbrook,et al.  Channel kinetics determine the time course of NMDA receptor-mediated synaptic currents , 1990, Nature.

[24]  M. Mayer,et al.  A kinetic analysis of the modulation of N‐methyl‐D‐aspartic acid receptors by glycine in mouse cultured hippocampal neurones. , 1990, The Journal of physiology.

[25]  D. Colquhoun,et al.  Rapid decay of averaged single-channel NMDA receptor activations recorded at low agonist concentration , 1992, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[26]  R. Nicoll,et al.  Analysis of excitatory synaptic action in pyramidal cells using whole‐cell recording from rat hippocampal slices. , 1990, The Journal of physiology.

[27]  C. Stevens,et al.  NMDA and non-NMDA receptors are co-localized at individual excitatory synapses in cultured rat hippocampus , 1989, Nature.

[28]  O. Krishtal,et al.  Excitatory amino acid receptors in hippocampal neurons: Kainate fails to desensitize them , 1986, Neuroscience Letters.

[29]  C. Cotman,et al.  Conformationally defined neurotransmitter analogues. Selective inhibition of glutamate uptake by one pyrrolidine-2,4-dicarboxylate diastereomer. , 1991, Journal of medicinal chemistry.

[30]  M. Mayer,et al.  Structure-activity relationships for amino acid transmitter candidates acting at N-methyl-D-aspartate and quisqualate receptors , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[31]  C. Nicholson,et al.  Ion diffusion modified by tortuosity and volume fraction in the extracellular microenvironment of the rat cerebellum. , 1981, The Journal of physiology.

[32]  D. Attwell,et al.  Electrogenic glutamate uptake is a major current carrier in the membrane of axolotl retinal glial cells , 1987, Nature.

[33]  D Colquhoun,et al.  Activation of N‐methyl‐D‐aspartate receptors by L‐glutamate in cells dissociated from adult rat hippocampus. , 1992, The Journal of physiology.

[34]  D. Attwell,et al.  Electrogenic glutamate uptake in glial cells is activated by intracellular potassium , 1988, Nature.

[35]  B. Gähwiler,et al.  Effects of the GABA uptake inhibitor tiagabine on inhibitory synaptic potentials in rat hippocampal slice cultures. , 1992, Journal of neurophysiology.

[36]  D. Attwell,et al.  Arachidonic acid induces a prolonged inhibition of glutamate uptake into glial cells , 1989, Nature.

[37]  L. Trussell,et al.  Glutamate receptor desensitization and its role in synaptic transmission , 1989, Neuron.

[38]  R. Silver,et al.  Rapid-time-course miniature and evoked excitatory currents at cerebellar synapses in situ , 1992, Nature.

[39]  Arne Schousboe,et al.  Transport and Metabolism of Glutamate and Gaba in Neurons and Glial Cells , 1981 .