 |
|||||
|
|||||
|
|||||
|
|||||
|
|||||
The Journal of Neuroscience, July 7, 2004, 24(27):6171-6180; doi:10.1523/JNEUROSCI.1380-04.2004
Previous Article | Next Article
Cellular/Molecular
Fast and Slow Voltage-Dependent Dynamics of Magnesium Block in the NMDA Receptor: The Asymmetric Trapping Block Model
Mariana Vargas-Caballero andHugh P. C. Robinson Department of Physiology, University of Cambridge, Cambridge, CB2 3EG, United Kingdom
The NMDA receptor (NMDAR) produces a long-lasting component of the glutamatergic EPSC in mammalian central neurons. The current through NMDARs is voltage dependent as a result of block by extracellular magnesium, which has recently been shown to give rise to a complex time dependence, with fast and slow components of responses to changes in membrane potential. Here, we studied the dynamics of block and unblock by measuring voltage step responses in conjunction with fast perfusion of agonist in nucleated patches isolated from rat cortical pyramidal neurons. We found that slow unblock shows a progressive onset during synaptic-like responses to brief pulses of agonist. Repolarizing briefly from +40 to -70 mV revealed that slow unblock is reestablished with a time constant of
5 msec at room temperature. Also, the time course of deactivation, in response to a pulse of agonist, slows twofold over the potential range -30 to +40 mV. An asymmetric "trapping block" model in which the voltage-independent closing rate constant of the blocked channel is approximately three times that of the unblocked channel accounts quantitatively for all of these phenomena and for responses to action potential waveform clamp. This model allows much more accurate prediction of NMDAR current in physiological conditions of magnesium concentration and changing membrane potential than previously possible. It suggests a positive allosteric link between occupation of the NMDAR pore by magnesium and closure of the permeation gate.
Key words: magnesium; open-channel block; synaptic integration; nucleated patch; kinetics; rat cortex
Received Dec 25, 2003; revised May 20, 2004; accepted May 20, 2004.
This article has been cited by other articles:
P. Ascher and L. Nowak
Early biophysics of the NMDA receptor channel
J. Physiol., October 1, 2009; 587(19): 4563 - 4564.
[Full Text] [PDF]
A. Polsky, B. Mel, and J. Schiller
Encoding and Decoding Bursts by NMDA Spikes in Basal Dendrites of Layer 5 Pyramidal Neurons
J. Neurosci., September 23, 2009; 29(38): 11891 - 11903.
[Abstract] [Full Text] [PDF]
A. J. Gibb
A tingle of extra excitement with voltage dependence of NMDA receptor activation
J. Physiol., December 1, 2008; 586(23): 5607 - 5607.
[Full Text] [PDF]
R. J. Clarke and J. W. Johnson
Voltage-dependent gating of NR1/2B NMDA receptors
J. Physiol., December 1, 2008; 586(23): 5727 - 5741.
[Abstract] [Full Text] [PDF]
R. J. Clarke and J. W. Johnson
NMDA Receptor NR2 Subunit Dependence of the Slow Component of Magnesium Unblock
J. Neurosci., May 24, 2006; 26(21): 5825 - 5834.
[Abstract] [Full Text] [PDF]
T. A. Blanpied, R. J. Clarke, and J. W. Johnson
Amantadine Inhibits NMDA Receptors by Accelerating Channel Closure during Channel Block
J. Neurosci., March 30, 2005; 25(13): 3312 - 3322.
[Abstract] [Full Text] [PDF]
A. Qian, A. L. Buller, and J. W. Johnson
NR2 subunit-dependence of NMDA receptor channel block by external Mg2+
J. Physiol., January 15, 2005; 562(2): 319 - 331.
[Abstract] [Full Text] [PDF]
|
|
|
|
 |
|