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

Subhrajit Bhattacharya; Alpa Khatri; Sharon A. Swanger; John O. DiRaddo; Feng Yi; Kasper B. Hansen; Hongjie Yuan; Stephen F. Traynelis

doi:10.1016/j.neuron.2018.06.010

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

Subhrajit Bhattacharya, Alpa Khatri, Sharon A. Swanger, John O. DiRaddo, Feng Yi, Kasper B. Hansen, Hongjie Yuan, Stephen F. Traynelis

Division of Biological and Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

60 Scopus citations

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. Bhattacharya et al. show that the NMDA receptor GluN2C subunit is preferentially incorporated into triheteromeric GluN1/GluN2A/GluN2C receptors in cerebellar granule cells. Triheteromeric GluN1/GluN2A/GluN2C receptors have single-channel properties that cannot be predicted from the composite subunits.

Original language	English
Pages (from-to)	315-328.e5
Journal	Neuron
Volume	99
Issue number	2
DOIs	https://doi.org/10.1016/j.neuron.2018.06.010
State	Published - Jul 25 2018

Funding

We thank Dr. T.J. Murphy for critical discussions, Dr. Kevin Ogden for development of single-channel analysis methods, and Phuong Le, Gil Shaulsky, and Dr. Jing Zhang for their outstanding technical support. This work was supported by the NIH ( NS036654 and NS065371 to S.F.T., GM103546 and NS097536 to K.B.H., NS086361 to S.A.S., and NS078873 to A.K.). S.F.T. is a member of the Scientific Advisory Board for Sage Therapeutics, principal investigator on a research grant to Emory University from Janssen, a consultant for Janssen, and a co-founder of NeurOp Inc.

Funder number
NS078873, NS086361, GM103546, NS036654, NS065371
R01NS097536

Keywords

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

Access to Document

10.1016/j.neuron.2018.06.010

Cite this

@article{81a02f21a6474df497a3caec6770ab84,

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

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. Bhattacharya et al. show that the NMDA receptor GluN2C subunit is preferentially incorporated into triheteromeric GluN1/GluN2A/GluN2C receptors in cerebellar granule cells. Triheteromeric GluN1/GluN2A/GluN2C receptors have single-channel properties that cannot be predicted from the composite subunits.",

keywords = "cerebellar granule cells, excitatory neurotransmission, ionotropic glutamate receptors, ligand-gated ion channel",

author = "Subhrajit Bhattacharya and Alpa Khatri and Swanger, \{Sharon A.\} and DiRaddo, \{John O.\} and Feng Yi and Hansen, \{Kasper B.\} and Hongjie Yuan and Traynelis, \{Stephen F.\}",

note = "Publisher Copyright: {\textcopyright} 2018 Elsevier Inc.",

year = "2018",

month = jul,

day = "25",

doi = "10.1016/j.neuron.2018.06.010",

language = "English",

volume = "99",

pages = "315--328.e5",

journal = "Neuron",

issn = "0896-6273",

publisher = "Cell Press",

number = "2",

}

TY - JOUR

T1 - Triheteromeric GluN1/GluN2A/GluN2C NMDARs with Unique Single-Channel Properties Are the Dominant Receptor Population in Cerebellar Granule Cells

AU - Bhattacharya, Subhrajit

AU - Khatri, Alpa

AU - Swanger, Sharon A.

AU - DiRaddo, John O.

AU - Yi, Feng

AU - Hansen, Kasper B.

AU - Yuan, Hongjie

AU - Traynelis, Stephen F.

PY - 2018/7/25

Y1 - 2018/7/25

N2 - 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. Bhattacharya et al. show that the NMDA receptor GluN2C subunit is preferentially incorporated into triheteromeric GluN1/GluN2A/GluN2C receptors in cerebellar granule cells. Triheteromeric GluN1/GluN2A/GluN2C receptors have single-channel properties that cannot be predicted from the composite subunits.

AB - 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. Bhattacharya et al. show that the NMDA receptor GluN2C subunit is preferentially incorporated into triheteromeric GluN1/GluN2A/GluN2C receptors in cerebellar granule cells. Triheteromeric GluN1/GluN2A/GluN2C receptors have single-channel properties that cannot be predicted from the composite subunits.

KW - cerebellar granule cells

KW - excitatory neurotransmission

KW - ionotropic glutamate receptors

KW - ligand-gated ion channel

UR - https://www.scopus.com/pages/publications/85049004500

U2 - 10.1016/j.neuron.2018.06.010

DO - 10.1016/j.neuron.2018.06.010

M3 - Article

C2 - 30056832

AN - SCOPUS:85049004500

SN - 0896-6273

VL - 99

SP - 315-328.e5

JO - Neuron

JF - Neuron

IS - 2

ER -

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

Abstract

Funding

Keywords

Access to Document

Other files and links

Fingerprint

Cite this