---
_id: '3807'
abstract:
- lang: eng
  text: The time course of Mg(2+) 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 Mg(2+) unblock were
    found to be non-instantaneous and complex, consisting of a prominent fast component
    (time constant approximately 100 micros) and slower components (time constants
    4 and approximately 300 ms), the relative amplitudes of which depended on the
    timing of the depolarizing pulse. Fitting a kinetic model to these data indicated
    that Mg(2+) 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 Mg(2+) 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 Mg(2+) unblock, indicating that
    slow Mg(2+) unblock of NMDAR channels makes the STDP timing window more precise.
author:
- first_name: Bjorn
  full_name: Kampa, Bjorn M
  last_name: Kampa
- first_name: John
  full_name: Clements, John
  last_name: Clements
- first_name: Peter M
  full_name: Peter Jonas
  id: 353C1B58-F248-11E8-B48F-1D18A9856A87
  last_name: Jonas
  orcid: 0000-0001-5001-4804
- first_name: Greg
  full_name: Stuart, Greg J
  last_name: Stuart
citation:
  ama: 'Kampa B, Clements J, Jonas PM, Stuart G. Kinetics of Mg(2+) unblock of NMDA
    receptors: implications for spike-timing dependent synaptic plasticity. <i>Journal
    of Physiology</i>. 2004;556(Pt 2):337-345. doi:<a href="https://doi.org/10.1113/jphysiol.2003.058842
    ">10.1113/jphysiol.2003.058842 </a>'
  apa: 'Kampa, B., Clements, J., Jonas, P. M., &#38; Stuart, G. (2004). Kinetics of
    Mg(2+) unblock of NMDA receptors: implications for spike-timing dependent synaptic
    plasticity. <i>Journal of Physiology</i>. Wiley-Blackwell. <a href="https://doi.org/10.1113/jphysiol.2003.058842
    ">https://doi.org/10.1113/jphysiol.2003.058842 </a>'
  chicago: 'Kampa, Bjorn, John Clements, Peter M Jonas, and Greg Stuart. “Kinetics
    of Mg(2+) Unblock of NMDA Receptors: Implications for Spike-Timing Dependent Synaptic
    Plasticity.” <i>Journal of Physiology</i>. Wiley-Blackwell, 2004. <a href="https://doi.org/10.1113/jphysiol.2003.058842
    ">https://doi.org/10.1113/jphysiol.2003.058842 </a>.'
  ieee: 'B. Kampa, J. Clements, P. M. Jonas, and G. Stuart, “Kinetics of Mg(2+) unblock
    of NMDA receptors: implications for spike-timing dependent synaptic plasticity,”
    <i>Journal of Physiology</i>, vol. 556, no. Pt 2. Wiley-Blackwell, pp. 337–45,
    2004.'
  ista: 'Kampa B, Clements J, Jonas PM, Stuart G. 2004. Kinetics of Mg(2+) unblock
    of NMDA receptors: implications for spike-timing dependent synaptic plasticity.
    Journal of Physiology. 556(Pt 2), 337–45.'
  mla: 'Kampa, Bjorn, et al. “Kinetics of Mg(2+) Unblock of NMDA Receptors: Implications
    for Spike-Timing Dependent Synaptic Plasticity.” <i>Journal of Physiology</i>,
    vol. 556, no. Pt 2, Wiley-Blackwell, 2004, pp. 337–45, doi:<a href="https://doi.org/10.1113/jphysiol.2003.058842
    ">10.1113/jphysiol.2003.058842 </a>.'
  short: B. Kampa, J. Clements, P.M. Jonas, G. Stuart, Journal of Physiology 556 (2004)
    337–45.
date_created: 2018-12-11T12:05:17Z
date_published: 2004-01-01T00:00:00Z
date_updated: 2021-01-12T07:52:20Z
day: '01'
doi: '10.1113/jphysiol.2003.058842 '
extern: 1
intvolume: '       556'
issue: Pt 2
main_file_link:
- open_access: '1'
  url: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1664940/
month: '01'
oa: 1
page: 337 - 45
publication: Journal of Physiology
publication_status: published
publisher: Wiley-Blackwell
publist_id: '2403'
quality_controlled: 0
status: public
title: 'Kinetics of Mg(2+) unblock of NMDA receptors: implications for spike-timing
  dependent synaptic plasticity'
type: journal_article
volume: 556
year: '2004'
...