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

摘要: Mammalian neurons contain at least three types of excitatory amino-acid receptors, selectively activated by N-methyl-D-aspartate (NMDA) or aspartate, (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionate ((S)-AMPA) and kainate. An important aspect NMDA receptors is their regulation a variety factors such as glycine, Mg2+ Zn2+ that are present in vivo. We show here receptor responses inhibited protons, with 50% inhibitory concentration (IC50) close to physiological pH, implying not fully active under normal conditions. (S)-AMPA kainate remain unchanged similar pH levels. Proton inhibition voltage-insensitive does result either from fast channel block, change conductance, an increase the (EC50) aspartate/NMDA glycine. Instead, protons seem decrease markedly opening frequency 30-50 pS channels, reduce relative proportion longer bursts. This feature could be relevant neurotoxic activation during ischaemia, well seizure generation, extracellular proton changes occur both these pathological situations. Furthermore, results may have implications for function transient synaptic transmission.