Reaction mechanism determines NMDA receptor response to repetitive stimulation

Gabriela Popescu; Antoine Robert; James R Howe; Anthony Auerbach

doi:10.1038/nature02775

Back

Reaction mechanism determines NMDA receptor response to repetitive stimulation

Journal article

Peer reviewed

Reaction mechanism determines NMDA receptor response to repetitive stimulation

Gabriela Popescu, Antoine Robert, James R Howe and Anthony Auerbach

Nature (London), Vol.430(7001), pp.790-793

08/12/2004

DOI: 10.1038/nature02775

PMID: 15306812

View Online

Abstract

At central excitatory synapses, N-methyl-D-aspartate (NMDA) receptors, which have a high affinity for glutamate, produce a slowly rising synaptic current in response to a single transmitter pulse and an additional current after a second, closely timed stimulus. Here we show, by examining the kinetics of transmitter binding and channel gating in single-channel currents from recombinant NR1/NR2A receptors, that the synaptic response to trains of impulses is determined by the molecular reaction mechanism of the receptor. The rate constants estimated for the activation reaction predict that, after binding neurotransmitter, receptors hesitate for approximately 4 ms in a closed high-affinity conformation before they either proceed towards opening or release neurotransmitter, with about equal probabilities. Because only about half of the initially fully occupied receptors become active, repetitive stimulation elicits currents with distinct waveforms depending on pulse frequency. This high-affinity/low-efficiency activation mechanism might serve as a link between stimulation frequency and the directionality of the ensuing synaptic plasticity.

Cell Line

Glutamic Acid - pharmacology

Humans

Receptors, N-Methyl-D-Aspartate - metabolism

Electrophysiology

Rats

Protein Subunits - metabolism

Receptors, N-Methyl-D-Aspartate - genetics

Dose-Response Relationship, Drug

Animals

Neuronal Plasticity

Glutamic Acid - metabolism

Kinetics

Protein Subunits - genetics

Details

Title: Subtitle: Reaction mechanism determines NMDA receptor response to repetitive stimulation
Creators: Gabriela Popescu - University at Buffalo, Department of Physiology and Biophysics and Center for Single Molecule Biophysics, Buffalo, New York 14214, USA. popescu@buffalo.edu
Antoine Robert
James R Howe
Anthony Auerbach
Resource Type: Journal article
Publication Details: Nature (London), Vol.430(7001), pp.790-793
Publisher: England
DOI: 10.1038/nature02775
PMID: 15306812
ISSN: 0028-0836
eISSN: 1476-4687
Grant note: F32 DA015164 / NIDA NIH HHS
Language: English
Date published: 08/12/2004
Academic Unit: Surgery
Record Identifier: 9984051765502771

Metrics

16 Record Views

109 Times Cited - Web of Science

See more details