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Neurotransmission

A new take on glutamate

Nature Reviews Neuroscience volume 11, page 732 (2010)Cite this article

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The authors performed whole-cell patch clamp recordings on cultured spinal neurons. Application of glutamate and a cocktail of glutamate receptor blockers potentiated GlyR-dependent inhibitory postsynaptic currents (identified by their sensitivity to the GlyR antagonist strychnine). The effect of glutamate was occluded by saturating doses of the competitive NMDAR inhibitor D(−)-2-amino-5-phosphonovaleric acid (AP5), suggesting that these ligands share a previously unknown binding site on the GlyR. Single-channel recordings indicated that potentiation of inhibitory transmission was mediated by increasing the frequency of GlyR channel opening.

To rule out a possible involvement of glutamate receptors in this effect on GlyR-mediated currents, the authors transfected recombinant human GlyRs into HEK293 cells, which lack glutamate receptors. Whole-cell recordings showed that glutamate alone had no effect on the membrane potential, confirming the absence of classic glutamatergic signalling. However, the amplitude of the inhibitory current produced by glycine administration was significantly increased by co-application of glutamate. These effects were mimicked by various glutamate-like ligands, including NMDA.

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ORIGINAL RESEARCH PAPER

  1. Liu, J., Wu, D. C. & Wang, Y. T. Allosteric potentiation of glycine receptor chloride currents by glutamate. Nature Neurosci. 12 Sep 2010 (doi:10.1038/nn.2633)

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  1. Katie Kingwell
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Kingwell, K. A new take on glutamate. Nat Rev Neurosci 11, 732 (2010). https://doi.org/10.1038/nrn2932

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