• DOI:10.1038/345347A0
• Corpus ID: 4351139

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}
}

• S. Traynelis, S. Cull-Candy
• Published 24 May 1990
• Biology
• Nature

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 concentration (IC50) that is close to physiological pH, implying that NMDA receptors are not fully active under normal conditions. (S)-AMPA and kainate responses remain unchanged at similar pH levels. Proton inhibition is voltage-insensitive and does not result either from fast channel block, a change in channel conductance, or an increase in the 50% excitatory concentration (EC50) of aspartate/NMDA or glycine. Instead, protons seem to decrease markedly the opening frequency of 30–50 pS NMDA channels, and reduce the relative proportion of longer bursts. This feature of NMDA receptors could be relevant to neurotoxic activation of NMDA receptors during ischaemia7, as well as to seizure generation, as extracellular proton changes occur during both of these pathological situations8,9. Furthermore, these results may have implications for normal NMDA receptor function as transient changes in extracellular protons occur during synaptic transmission8,10.