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Triheteromeric NMDA Receptors at Hippocampal Synapses

Tovar, Kenneth R and McGinley, Matthew J and Westbrookl, Gary L (2013) Triheteromeric NMDA Receptors at Hippocampal Synapses. Journal of Neuroscience.

Abstract

NMDA receptors are composed of two N1 and two N2 subunits. Constituent N2
subunits control pharmacological and kinetic characteristics of the receptor. Although
NMDA receptors in hippocampal or cortical neurons are often thought of as
diheteromeric, containing only one type of N2 subunit, triheteromeric receptors with
more than one type of N2 subunit also have been reported. However, the relative
contribution of di- and triheteromeric NMDA receptors at synapses has been difficult to
assess. Because wild-type hippocampal principal neurons express N1, N2A and N2B,
we used cultured hippocampal principal neurons from N2A and N2B-knockout mice as
templates for diheteromeric synaptic receptors. Summation of N1/N2B and N1/N2A
excitatory postsynaptic currents (EPSCs) could not account for the deactivation kinetics
of wild-type EPSCs however. To make a quantitative estimate of NMDA receptor
subtypes at wild-type synapses, we used the deactivation kinetics, as well as the effects
of the competitive antagonist NVP-AAM077. Our results indicate that three types of
NMDA receptors contribute to the wild-type EPSC, with at least two-thirds being
triheteromeric receptors. Functional isolation of synaptic triheteromeric receptors
revealed deactivation kinetics and pharmacology distinct from either diheteromeric
receptor subtype. Because of differences in open probability, synaptic triheteromeric
receptors outnumbered N1/N2A receptors by 5.8 to 1 and N1/N2B receptors by 3.2 to
2
1. Our results suggest that triheteromeric NMDA receptors must be either preferentially
assembled or preferentially localized at synapses.

Item Type: Article
Keywords: NMDA receptor NMDA subunits GluN1 GluN2A GluN2B
Date Deposited: 26 Apr 2016 23:46
Last Modified: 26 Apr 2016 23:46
URI: https://oak.novartis.com/id/eprint/9752

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