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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.

Author information

1
Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322, USA.
2
Department of Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, MT 59812, USA.
3
Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322, USA. Electronic address: strayne@emory.edu.

Abstract

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.

KEYWORDS:

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

PMID:
30056832
PMCID:
PMC6090556
[Available on 2019-07-25]
DOI:
10.1016/j.neuron.2018.06.010

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