Voltage dependence of NMDA-activated macroscopic conductances predicted by single-channel kinetics

@inproceedings{Jahr1990VoltageDO,
  title={Voltage dependence of NMDA-activated macroscopic conductances predicted by single-channel kinetics},
  author={CE Jahr and Cf Stevens},
  booktitle={Journal of Neuroscience},
  year={1990}
}
The conductance activated in many mammalian CNS neurons by the glutamate analog NMDA is inhibited at hyperpolarized potentials by extracellular magnesium. Whole-cell recordings from hippocampal neurons in culture were used to determine the voltage dependence of the NMDA conductance in the presence of extracellular magnesium concentrations from 1 microM to 10 mM. The conductance-voltage data are well fitted by a gating function derived from rate constants determined in an earlier study of the… 

Figures and Tables from this paper

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References

SHOWING 1-7 OF 7 REFERENCES

A quantitative description of NMDA receptor-channel kinetic behavior

  • CE JahrC. Stevens
  • Biology
    The Journal of neuroscience : the official journal of the Society for Neuroscience
  • 1990
Evaluation of the blocking rates over Mg concentrations from 0.2–200 microM indicate that a single “blocking” mechanism cannot account for the short closed states and that a second voltage-dependent but Mg-independent “blocked” state is necessary to explain the data especially at low M g concentrations.

Magnesium gates glutamate-activated channels in mouse central neurones

The voltage dependence of the NMDA receptor-linked conductance appears to be a consequence of the voltage dependenceof the Mg2+ block and its interpretation does not require the implication of an intramembrane voltage-dependent ‘gate’.

Glycine potentiates the NMDA response in cultured mouse brain neurons

G glycine may facilitate excitatory transmission in the brain through an allosteric activation of the NMDA receptor, and can be observed in outside-out patches as an increase in the frequency of opening of the channels activated by NMDA agonists.

The effects of L-glutamate and its analogues upon the membrane conductance of central murine neurones in culture.

The primary effect was depolarization accomplished by an apparent decrease of neurone input conductance (Gm), which favoured the electrogenesis of regenerative potentials that were insensitive to tetrodotoxin.

Voltaae - deoendent block by ‘ Mg 2 + of NMDA iesponses in spinal cbrd neur & es

  • 1984

Voltaae-deoendent block by 'Mg2+ of NMDA iesponses in spinal cbrd neur&es

  • Nature
  • 1984

The effects of L-glutamate

  • 1982