Skip navigation
Skip navigation

Kinetics of Mg2+ unblock of NMDA receptors: implications for spike-timing dependent synaptic plasticity

Kampa, Bjoern; Clements, John D; Jonas, P; Stuart, Gregory J

Description

The time course of Mg2+ block and unblock of NMDA receptors (NMDARs) determines the extent they are activated by depolarization. Here, we directly measure the rate of NMDAR channel opening in response to depolarizations at different times after brief (1 ms) and sustained (4.6 s) applications of glutamate to nucleated patches from neocortical pyramidal neurons. The kinetics of Mg2+ unblock were found to be non-instantaneous and complex, consisting of a prominent fast component (time constant ∼...[Show more]

dc.contributor.authorKampa, Bjoern
dc.contributor.authorClements, John D
dc.contributor.authorJonas, P
dc.contributor.authorStuart, Gregory J
dc.date.accessioned2015-12-13T22:51:02Z
dc.date.available2015-12-13T22:51:02Z
dc.identifier.issn0022-3751
dc.identifier.urihttp://hdl.handle.net/1885/81083
dc.description.abstractThe time course of Mg2+ block and unblock of NMDA receptors (NMDARs) determines the extent they are activated by depolarization. Here, we directly measure the rate of NMDAR channel opening in response to depolarizations at different times after brief (1 ms) and sustained (4.6 s) applications of glutamate to nucleated patches from neocortical pyramidal neurons. The kinetics of Mg2+ unblock were found to be non-instantaneous and complex, consisting of a prominent fast component (time constant ∼ 100 μs) and slower components (time constants 4 and ∼ 300 ms), the relative amplitudes of which depended on the timing of the depolarizing pulse. Fitting a kinetic model to these data indicated that Mg2+ not only blocks the NMDAR channel, but reduces both the open probability and affinity for glutamate, while enhancing desensitization. These effects slow the rate of NMDAR channel opening in response to depolarization in a time-dependent manner such that the slower components of Mg2+ unblock are enhanced during depolarizations at later times after glutamate application. One physiological consequence of this is that brief depolarizations occurring earlier in time after glutamate application are better able to open NMDAR channels. This finding has important implications for spike-timing-dependent synaptic plasticity (STDP), where the precise (millisecond) timing of action potentials relative to synaptic inputs determines the magnitude and sign of changes in synaptic strength. Indeed, we find that STDP timing curves of NMDAR channel activation elicited by realistic dendritic action potential waveforms are narrower than expected assuming instantaneous Mg2+ unblock, indicating that slow Mg2+ unblock of NMDAR channels makes the STDP timing window more precise.
dc.publisherCambridge University Press
dc.sourceJournal of Physiology
dc.subjectKeywords: glutamic acid; magnesium ion; n methyl dextro aspartic acid receptor; glutamic acid; magnesium; n methyl dextro aspartic acid receptor; accuracy; action potential; animal cell; animal tissue; article; binding affinity; controlled study; dendrite; depolari
dc.titleKinetics of Mg2+ unblock of NMDA receptors: implications for spike-timing dependent synaptic plasticity
dc.typeJournal article
local.description.notesImported from ARIES
local.description.refereedYes
local.identifier.citationvolume556
dc.date.issued2004
local.identifier.absfor110902 - Cellular Nervous System
local.identifier.ariespublicationMigratedxPub9414
local.type.statusPublished Version
local.contributor.affiliationKampa, Bjoern, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationClements, John D, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationJonas, P, University of Freiburg
local.contributor.affiliationStuart, Gregory J, College of Medicine, Biology and Environment, ANU
local.bibliographicCitation.issue2
local.bibliographicCitation.startpage337
local.bibliographicCitation.lastpage345
local.identifier.doi10.1113/jphysiol.2003.058842
dc.date.updated2015-12-11T10:43:42Z
local.identifier.scopusID2-s2.0-2342467434
CollectionsANU Research Publications

Download

There are no files associated with this item.


Items in Open Research are protected by copyright, with all rights reserved, unless otherwise indicated.

Updated:  17 November 2022/ Responsible Officer:  University Librarian/ Page Contact:  Library Systems & Web Coordinator