Polymodal regulation of NMDA receptor channels.
Glutamate-activated N-methyl-D-aspartate (NMDA) receptors are ligand-gated ion channels, which mediate synaptic transmission, long-term potentiation, synaptic plasticity and neurodegeneration via conditional Ca(2+) signalling. Recent crystallographic studies have focussed on solving the structural determinant of the ligand binding within the core region of NR1 and NR2 subunits. Future structural analysis will help to understand the mechanism of native channel activation and regulation during synaptic transmission. A number of NMDA receptor ligands have been identified which act as positive or negative modulators of receptor function. There is evidence that the lipid bilayer can further regulate the activity of the NMDA receptor channels. Modulators of NMDA receptor function offer the potential for the development of novel therapeutics to target neurological disorders associated with this family of glutamate ion channel receptors. Here, we review the recent literature concerning structural and functional properties, as well as the physiological and pathological roles of NMDA receptor channels.
Kloda
Anna
A
School of Biomedical Sciences, The University of Queensland, Brisbane, Queensland, Australia.
Martinac
Boris
B
Adams
David J
DJ
D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D018360:Crystallography, X-Ray / Q000379:methods; D006801:Humans; D007473:Ion Channels / Q000737:chemistry; D008024:Ligands; D008051:Lipid Bilayers / Q000737:chemistry; D008954:Models, Biological; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011485:Protein Binding; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction
D007473:Ion Channels; D008024:Ligands; D008051:Lipid Bilayers; D016194:Receptors, N-Methyl-D-Aspartate; D002118:Calcium