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.
N1 - Publisher Copyright:
© 2018 Elsevier Inc.
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 - http://www.scopus.com/inward/record.url?scp=85049004500&partnerID=8YFLogxK
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 -