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Neuron. 2018 Jul 25;99(2):315-328.e5. doi: 10.1016/j.neuron.2018.06.010. Epub 2018 Jun 28.

Triheteromeric GluN1/GluN2A/GluN2C NMDARs with Unique Single-Channel Properties Are the Dominant Receptor Population in Cerebellar Granule Cells.

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Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Department of Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, MT 59812, USA.
Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322, USA. Electronic address:


NMDA-type glutamate receptors (NMDARs) are ligand-gated ion channels that mediate excitatory neurotransmission in the CNS. Here we describe functional and single-channel properties of triheteromeric GluN1/GluN2A/GluN2C receptors, which contain two GluN1, one GluN2A, and one GluN2C subunits. This NMDAR has three conductance levels and opens in bursts similar to GluN1/GluN2A receptors but with a single-channel open time and open probability reminiscent of GluN1/GluN2C receptors. The deactivation time course of GluN1/GluN2A/GluN2C receptors is intermediate to GluN1/GluN2A and GluN1/GluN2C receptors and is not dominated by GluN2A or GluN2C. We show that triheteromeric GluN1/GluN2A/GluN2C receptors are the predominant NMDARs in cerebellar granule cells and propose that co-expression of GluN2A and GluN2C in cerebellar granule cells occludes cell surface expression of diheteromeric GluN1/GluN2C receptors. This new insight into neuronal GluN1/GluN2A/GluN2C receptors highlights the complexity of NMDAR signaling in the CNS.


cerebellar granule cells; excitatory neurotransmission; ionotropic glutamate receptors; ligand-gated ion channel

[Available on 2019-07-25]

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