A quantitative description of NMDA receptor-channel kinetic behavior

@inproceedings{Jahr1990AQD,
  title={A quantitative description of NMDA receptor-channel kinetic behavior},
  author={Craig E. Jahr and Charles F. Stevens},
  booktitle={The Journal of neuroscience : the official journal of the Society for Neuroscience},
  year={1990}
}
  • C. Jahr, C. Stevens
  • Published in
    The Journal of neuroscience…
    1990
  • Chemistry, Medicine
Currents evoked in neurons of the vertebrate CNS by the glutamate agonist N-methyl-D-aspartate (NMDA) exhibit a marked voltage dependence in the presence of extracellular Mg. At the single-channel level, the addition of external Mg alters single-channel openings from long-lived events to many very short events grouped into bursts of openings. These bursts apparently result from short interruptions of current flow during periods when the channel is in the open configuration. Single- channel… Expand
Voltage dependence of NMDA-activated macroscopic conductances predicted by single-channel kinetics
  • C. Jahr, C. Stevens
  • Chemistry, Medicine
  • The Journal of neuroscience : the official journal of the Society for Neuroscience
  • 1990
TLDR
The conductance activated in many mammalian CNS neurons by the glutamate analog NMDA is inhibited at hyperpolarized potentials by extracellular magnesium, consistent with the assumption that magnesium inhibits current through the NMDA-activated channel by directly blocking the ion pore. Expand
Blocker Studies of the Functional Architecture of the NMDA Receptor Channel
TLDR
These experiments showed that the apparent affinity of the blocker for the channel depended not only on the microscopic equilibrium dissociation constant (Kd), but also on the number of blocker binding sites, their mutual influences, and, of particular importance, the interaction of the blockers with the gating structures of the channel. Expand
Two-component blocking kinetics of open NMDA channels by organic cations.
  • A. Sobolevsky
  • Chemistry, Medicine
  • Biochimica et biophysica acta
  • 1999
TLDR
NMDA receptor channel responses were recorded from acutely isolated rat hippocampal neurons, using whole-cell patch-clamp techniques and it was established that depending on the behavior of the amplitude of the fast component for the recovery kinetics, the blocker action can be assigned to one of five types described by the simplest models. Expand
Slow voltage-dependent changes in channel open-state probability underlie hysteresis of NMDA responses in Mg2+-free solutions
TLDR
It is discovered that N-methyl-D-aspartate channels in excised patches reversibly shifted their open-state probability (Po) in a voltage-dependent way, exhibiting approximately 3- to 4-fold greater Po at positive potentials than at rest. Expand
Kinetics of Mg2+ unblock of NMDA receptors: implications for spike‐timing dependent synaptic plasticity
TLDR
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, which has important implications for spike‐timing‐dependent synaptic plasticity (STDP). Expand
NMDA receptor activation by spontaneous glutamatergic neurotransmission.
TLDR
Results indicate that NMDA receptors significantly contribute to signaling at rest in the absence of dendritic depolarizations or concomitant AMPA receptor activity. Expand
On the kinetics of NMDA-associated ion channels : different agonists and the effects of anaesthetic drugs
The majority of studies to date dealing with NMDAactivated ion channels have used whole-cell preparations to study macroscopic currents. The whole-cell current response to applied agonists consistsExpand
Effects of intracellular Mg2+ on channel gating and steady‐state responses of the NMDA receptor in cultured rat neurons.
TLDR
A four‐state model in which the NMDA‐activated channel can close while blocked by Mgi2+ is proposed, and it is estimated that the rate of channel opening is increased by a factor of 1.4 when Mg2+ occupies the channel. Expand
Burst kinetics of single NMDA receptor currents in cell‐attached patches from rat brain cortical neurons in culture.
TLDR
Each opening in bursts of two or more openings is kinetically similar to every other opening regardless of burst length, and a kinetic model with three open and four closed intraburst states is shown to be consistent with these results. Expand
Modal gating of NMDA receptors and the shape of their synaptic response
TLDR
Simulations indicate that native NMDAR-mediated synaptic responses arise mainly from the most common mode, and that the slow rise and decay of the current can be attributed to multiple transitions between fully liganded open and closed states rather than to agonist dissociation. Expand
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