N-methyl-D-aspartic acid receptor structure and function

McBain, Christopher J.; Mayer, Moriz

doi:10.1152/physrev.1994.74.3.723

Cited by 892 publications

(613 citation statements)

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“…It is unclear why behavioral deficits are so pronounced during this and not other postnatal exposure periods, however one hypothesis involves the altered subunit composition of the NMDA receptor during development. NMDARs are heteromeric tetramers (McBain & Mayer, 1994;Schorge and Colquhoun 2003), composed of both NR1 and NR2 subunits. NR1 subunits are ubiquitous in brain, and expressed as at least eight splice variants (Zukin & Bennett, 1995).…”

Section: Discussionmentioning

confidence: 99%

Agmatine reduces balance deficits in a rat model of third trimester binge-like ethanol exposure

Lewis

Wellmann

Barron

2007

Pharmacology Biochemistry and Behavior

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This study examined the effects of binge-like ethanol (ETOH) exposure in neonatal rats on a cerebellar-mediated balance task, and the ability of agmatine, an n-methyl-d-aspartate receptor (NMDAR) modulator, to reverse such effects. Five neonatal treatments groups were used, including ETOH (6.0 g/kg/day), AG (20 mg/kg), ETOH plus AG (6.0 g/kg/day and 20 mg/kg), a maltose control, and a non-treated control. Ethanol was administered via oral intubation twice daily for eight days, (AG was administered with the last ETOH intubation only). Two exposure periods were used; PND 1-8 or PND 8-15. On PND 31-33, balance performance on a single dowel was tested. Treatment with AG during withdrawal in ETOH exposed animals improved performance relative to ETOH alone among the PND 1-8 exposure period. ETOH exposure during the 2 nd postnatal week did not impair balance. These findings provide further support that exposure to ETOH during critical developmental periods can impair performance on a cerebellar-dependent balance task. Of perhaps greater significance, co-administration of agmatine reduced these deficits suggesting that NMDA modulation via polyamine blockade may provide a novel approach to attenuating damage associated with binge-like ETOH consumption.

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Section: Discussionmentioning

confidence: 99%

Agmatine reduces balance deficits in a rat model of third trimester binge-like ethanol exposure

Lewis

Wellmann

Barron

2007

Pharmacology Biochemistry and Behavior

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“…All iGluRs can form heteromeric subunit assemblies, composed of different subunits, which have different physiological and pharmacological properties and are differentially distributed throughout the CNS 25,50,237,[250][251][252][253] . Both AMPA 254 and NMDA receptors 255 are probably largely formed from tetrameric, heteromeric assemblies of different subunits 256 .…”

Section: The Iglur Family Is Classified Into Three Major Subtypes a Cmentioning

confidence: 99%

“…3) NMDA receptors The NMDA receptor is perhaps the best characterized of the iGluR 251,314 , in part due to the existence of selective agonists and antagonists. NMDA receptors are ubiquitous 315 and are found with relative ease in the cerebral cortex within the Schaffer collaterals of the CA3 -CA1 projection within the hippocampus.…”

Section: ) Synaptic Plasticitymentioning

confidence: 99%

A Review of Glutamate Receptors I: Current Understanding of Their Biology

Rousseaux

2008

J Toxicol Pathol

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Seventy years ago it was discovered that glutamate is abundant in the brain and that it plays a central role in brain metabolism. However, it took the scientific community a long time to realize that glutamate also acts as a neurotransmitter. Glutamate is an amino acid and brain tissue contains as much as 5 -15 mM glutamate per kg depending on the region, which is more than of any other amino acid. The main motivation for the ongoing research on glutamate is due to the role of glutamate in the signal transduction in the nervous systems of apparently all complex living organisms, including man. Glutamate is considered to be the major mediator of excitatory signals in the mammalian central nervous system and is involved in most aspects of normal brain function including cognition, memory and learning. In this review, the basic biology of the excitatory amino acids glutamate, glutamate receptors, GABA, and glycine will first be explored. In the second part of this review, the known pathophysiology and pathology will be described. (J Toxicol Pathol 2008; 21: 25-51)

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“…Glutamate is involved in normal as well as pathological brain function and plays a key role in fast synaptic transmission. Glutamate binds to ionotropic glutamate receptors (GluRs), which can be divided into three classes according to their pharmacology, molecular structure, and biophysical properties: AMPA, kainate, and NMDA receptors (McBain and Mayer, 1994;Dingledine et al, 1999;Erreger et al, 2004). Overstimulation of NMDA receptors by the extracellular glutamate that accumulates under ischemic conditions (such as during stroke) can lead to cytotoxic levels of Ca 2ϩ and other divalent ions within neurons.…”

Section: Introductionmentioning

confidence: 99%

Protons Trap NR1/NR2B NMDA Receptors in a Nonconducting State

Banke¹,

Dravid²,

Traynelis³

2005

J. Neurosci.

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NMDA receptors are highly expressed in the CNS and are involved in excitatory synaptic transmission, as well as synaptic plasticity. Given that overstimulation of NMDA receptors can cause cell death, it is not surprising that these channels are under tight control by a series of inhibitory extracellular ions, including zinc, magnesium, and H ϩ . We studied the inhibition by extracellular protons of recombinant NMDA receptor NR1/NR2B single-channel and macroscopic responses in transiently transfected human embryonic kidney HEK 293 cells using patch-clamp techniques. We report that proton inhibition proceeds identically in the absence or presence of agonist, which rules out the possibility that protonation inhibits receptors by altering coagonist binding. The response of macroscopic currents in excised patches to rapid jumps in pH was used to estimate the microscopic association and dissociation rates for protons, which were 1.4 ϫ 10 9 M Ϫ1 sec Ϫ1 and 110 -196 sec Ϫ1 , respectively (K d corresponds to pH 7.2). Protons reduce the open probability without altering the time course of desensitization or deactivation. Protons appear to slow at least one time constant describing the intra-activation shut-time histogram and modestly reduce channel open time, which we interpret to reflect a reduction in the overall channel activation rate and possible proton-induced termination of openings. This is consistent with a modest proton-dependent slowing of the macroscopic response rise time. From these data, we propose a physical model of proton inhibition that can describe macroscopic and single-channel properties of NMDA receptor function over a range of pH values.

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N-methyl-D-aspartic acid receptor structure and function

Cited by 892 publications

References 0 publications

Agmatine reduces balance deficits in a rat model of third trimester binge-like ethanol exposure

Agmatine reduces balance deficits in a rat model of third trimester binge-like ethanol exposure

A Review of Glutamate Receptors I: Current Understanding of Their Biology

Protons Trap NR1/NR2B NMDA Receptors in a Nonconducting State

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