Abstract：
:Excitatory neurotransmission mediated by N-methyl-d-aspartate receptors (NMDARs) is fundamental to learning and memory and, when impaired, causes certain neurological disorders. NMDARs are heterotetrameric complexes composed of two GluN1 [NR1] and two GluN2(A-D) [NR2(A-D)] subunits. The GluN2 subunit is responsible for subunit-specific channel activity and gating kinetics including activation (rise time), peak open probability (peak Po) and deactivation (decay time). The peak Po of recombinant NMDARs was recently described to be controlled by the extracellular GluN2 N-terminal domain (NTD). The cytoplasmic GluN2 C-terminal domain (CTD) could also be involved, because the Po of synaptic NMDARs is reduced in mice expressing C-terminally truncated GluN2 subunits. Here, we examined the role of the GluN2 cytoplasmic tail for NMDAR channel activity and gating in HEK-293 cells. C-terminal truncation of GluN2A, GluN2B or GluN2C did not change the subunit-specific rise time but accelerated the decay time of glutamate-activated currents. Furthermore, the peak Po was reduced by about 50% for GluN2A and GluN2B but not for GluN2C. These results indicated that the CTD of GluN2 has a modulating role in NMDAR gating even in the absence of interacting synaptic proteins. Reduction of peak Po and deactivation kinetics following GluN2 C-terminal truncation were reversed by re-introducing a CTD from a different GluN2 subunit. Thus, the CTDs of GluN2 subunits behave as constitutive structural elements required for normal functioning of NMDARs but are not involved in determining the subunit-specific gating properties of NMDARs.
journal_name
Neuropharmacologyjournal_title
Neuropharmacologyauthors
Punnakkal P,Jendritza P,Köhr Gdoi
10.1016/j.neuropharm.2011.12.018subject
Has Abstractpub_date
2012-04-01 00:00:00pages
1985-92issue
5-6eissn
0028-3908issn
1873-7064pii
S0028-3908(11)00575-2journal_volume
62pub_type
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