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A false transmitter at excitatory synapses

Z Z Pan1, G Tong, C E Jahr

  • 1Vollum Institute, Oregon Health Sciences University L474, Portland 97201-3098.

Neuron
|July 1, 1993
PubMed
Summary
This summary is machine-generated.

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D-glutamate, a false transmitter, dramatically shortens N-methyl-D-aspartate receptor activation times in neurons. This indicates neurotransmitter unbinding rates control synaptic response speed and transient elevations in synaptic clefts.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Synaptic Transmission

Background:

  • N-methyl-D-aspartate (NMDA) receptors are crucial for synaptic plasticity and neurotransmission.
  • The kinetics of NMDA receptor activation influence neuronal signaling and information processing.

Purpose of the Study:

  • To investigate the time course of synaptic activation of NMDA receptors using a low-affinity agonist.
  • To determine the role of neurotransmitter unbinding rates in shaping NMDA receptor-mediated postsynaptic currents.

Main Methods:

  • Utilized cultured hippocampal neurons loaded with D-glutamate, a low-affinity NMDA receptor agonist.
  • Stimulated neurons to evoke NMDA receptor excitatory postsynaptic currents (EPSCs) via autaptic connections.
  • Recorded NMDA receptor currents in outside-out patches with brief D-glutamate applications.

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Main Results:

  • Repetitive stimulation with D-glutamate significantly shortened both the rising and decaying phases of NMDA receptor EPSCs.
  • The observed EPSC time course was replicated by brief (1-4 ms) applications of D-glutamate in patch recordings.
  • D-glutamate acted as a false transmitter, revealing insights into natural neurotransmitter dynamics.

Conclusions:

  • The slow unbinding rate of the natural neurotransmitter is a primary determinant of NMDA receptor EPSC kinetics.
  • Free neurotransmitter concentration in the synaptic cleft is elevated for only a few milliseconds post-release.
  • These findings elucidate the mechanisms controlling synaptic activation speed and neurotransmitter dynamics.