Homocysteine reduces NMDAR desensitization and differentially modulates peak amplitude of NMDAR currents, depending on GluN2 subunit composition.

Abstract:

:N-methyl-d-aspartate receptors (NMDARs) have been linked to schizophrenia because agents that bind the receptor, like ketamine and phencyclidine, are capable of inducing schizophrenia-like symptoms. Here we show that the amino acid homocysteine (HCY), which is increased in the blood of schizophrenia patients, reduces desensitization of NMDARs in cultured mouse neurons, human embryonic kidney cells transfected with GluN1 + GluN2A, GluN2B, or GluN2D subunits, and hippocampal slices. HCY also alters the peak amplitude of NMDAR currents, depending on the GluN2 subunit the receptor contains; GluN1 + GluN2A-containing NMDARs show an increase in peak amplitude when exposed to HCY, while GluN1 + GluN2B-containing NMDARs show a decrease in peak amplitude. Both peak amplitude and desensitization effects of HCY can be occluded by saturating the NMDAR with glycine. Since glycine concentrations are not saturating in the brain, HCY could play an NMDAR-modulating role in the nervous system. We also show that HCY shares characteristics with glutamate and suggest that HCY affects both the agonist and co-agonist site of the NMDAR.

journal_name

J Neurophysiol

authors

Bolton AD,Phillips MA,Constantine-Paton M

doi

10.1152/jn.00809.2012

subject

Has Abstract

pub_date

2013-10-01 00:00:00

pages

1567-82

issue

7

eissn

0022-3077

issn

1522-1598

pii

jn.00809.2012

journal_volume

110

pub_type

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