Glycine Gating of NR1/NR2A NMDA Receptors

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Glycine-dependent activation of NMDA receptors

N-methyl-d-aspartate (NMDA) receptors are the only neurotransmitter receptors whose activation requires two distinct agonists. Heterotetramers of two GluN1 and two GluN2 subunits, NMDA receptors are broadly distributed in the central nervous system, where they mediate excitatory currents in response to synaptic glutamate release. Pore opening depends on the concurrent presence of glycine, which...

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Gating reaction mechanism of neuronal NMDA receptors.

The activation mechanisms of recombinant N-methyl-d-aspartate receptors (NRs) have been established in sufficient detail to account for their single channel and macroscopic responses; however, the reaction mechanism of native NRs remains uncertain due to indetermination of the isoforms expressed and possible neuron-specific factors. To delineate the activation mechanism of native NRs, we examin...

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Glycine potentiates strychnine-induced convulsions: role of NMDA receptors.

Strychnine poisoning leads to seizures that have traditionally been attributed to competitive antagonism of glycine receptors in the spinal cord. Although glycine is thought to act as an inhibitory neurotransmitter, a strychnine-insensitive glycine (Gly2) receptor has been recently described in cultured mouse neurons that is thought to be allosterically linked to the excitatory amino acid NMDA ...

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Subunit-selective allosteric inhibition of glycine binding to NMDA receptors.

NMDA receptors are ligand-gated ion channels that mediate excitatory neurotransmission in the brain and are involved in numerous neuropathological conditions. NMDA receptors are activated upon simultaneous binding of coagonists glycine and glutamate to the GluN1 and GluN2 subunits, respectively. Subunit-selective modulation of NMDA receptor function by ligand binding to modulatory sites distinc...

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In this issue, Papouin et al. show that glycine is the endogenous coagonist for extrasynaptic NMDA receptors (NMDARs), unlike at synapses where the coagonist is d-serine. By enzymatically degrading endogenous glycine, they begin to address the enigmatic physiological and pathological roles for extrasynaptic NMDARs.

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ژورنال

عنوان ژورنال: Biophysical Journal

سال: 2013

ISSN: 0006-3495

DOI: 10.1016/j.bpj.2012.11.1530