Proton inhibition of N-methyl-D-aspartate receptors in cerebellar neurons

@article{Traynelis1990ProtonIO,
  title={Proton inhibition of N-methyl-D-aspartate receptors in cerebellar neurons},
  author={Stephen F. Traynelis and Stuart G. Cull-Candy},
  journal={Nature},
  year={1990},
  volume={345},
  pages={347-350}
}
MAMMALIAN neurons contain at least three types of excitatory amino-acid receptors, selectively activated by N-methyl-D-aspar-tate (NMDA) or aspartate, (S)-α-amino-3-hydroxy-5-methyl-4-isoxazole proprionate ((S)-AMPA) and kainate1. An important aspect of NMDA receptors is their regulation by a variety of factors such as glycine2, Mg2+ (refs. 3,4) and Zn2+ (refs 5,6) that are present in vivo. We show here that NMDA receptor responses are selectively inhibited by protons, with a 50% inhibitory… 
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TLDR
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TLDR
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TLDR
Currents gated by δ2(A654T) were sensitive to the extracellular pH, being smaller at acidic than at alkaline pH, with a pH IC50 value of 7.47 and a maximum inhibition of 70%.
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TLDR
Electroneutral substitutions at this position restored pH sensitivity and, consequently, polyamine relief of tonic inhibition, suggesting that exon 5 may act as a tethered pH-sensitive constitutive modulator of NMDA receptor function.
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TLDR
The ability of zinc to specifically modulate postsynaptic neuronal responses to excitatory amino acid transmitters, reducing N-methyl-to-aspartate receptor-mediated excitation while often increasing quisqualate receptor's excitation, is proposed to underlie its normal function at central exciteatory synapses and furthermore could be relevant to neuronal cell loss in certain disease states.
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TLDR
Using voltage-clamp experiments on mouse spinal cord neurones, it is shown that the voltage-sensitivity of NMDA action is greatly reduced on the withdrawal of physiological concentrations (∼1 mM) of Mg2+ from the extracellular fluid, providing further evidence that Mg 2+ blocks inward current flow through ion channels linked to NMDA receptors.
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TLDR
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’.
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TLDR
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.
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TLDR
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TLDR
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TLDR
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TLDR
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