The glycine site modulates NMDA-mediated changes of intracellular free calcium in cultures of hippocampal neurons.

Abstract:

:Recent evidence indicates that the N-methyl-D-aspartate (NMDA) receptor-channel complex contains a glycine subunit whose activation may be necessary for channel operation. It has been previously shown that stimulation of the NMDA receptor leads to an increase in intracellular ionic Ca2+ [( Ca2+]i); therefore, we examined the role of the NMDA receptor-associated glycine site in modulating [Ca2+]i using the fluorescent dye Fura II in hippocampal neuron cultures. A 3-s pulse of 200 microM NMDA resulted in a mean [Ca2+]i increase of 363 nM above the average resting concentration of 122 nM. Perfusion of the glycine site antagonist 7-chlorokynurenate (Cl-Kyn) essentially eliminated the NMDA-induced alteration in [Ca2+]i. Either 40 microM glycine or 50 microM D-serine completely reversed the effect of Cl-Kyn, indicating that the drug was acting at the glycine site. The NMDA receptor antagonists 2-amino-5-phosphonovalerate (AP5) and ketamine, which bind to the glutamate recognition site and the ion channel, respectively, also blocked the NMDA-mediated [Ca2+]i response; however, glycine or D-serine did not reverse this effect. These data show that the glycine binding site coupled to the NMDA receptor modulates the NMDA-mediated increase in [Ca2+]i. Antagonists of the glycine site provide a new tool to investigate and possibly control neuroplasticity and neurotoxicity related to the NMDA receptor complex.

journal_name

Neurosci Lett

journal_title

Neuroscience letters

authors

Oliver MW,Shacklock JA,Kessler M,Lynch G,Baimbridge KG

doi

10.1016/0304-3940(90)90071-g

subject

Has Abstract

pub_date

1990-07-03 00:00:00

pages

197-202

issue

2

eissn

0304-3940

issn

1872-7972

pii

0304-3940(90)90071-G

journal_volume

114

pub_type

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