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CONTROL BY ASPARAGINE RESIDUES OF CALCIUM PERMEABILITY AND MAGNESIUM BLOCKADE IN THE NMDA RECEPTOR

BURNASHEV, N; SCHOEPFER, R; MONYER, H; RUPPERSBERG, JP; GUNTHER, W; SEEBURG, PH; SAKMANN, B; (1992) CONTROL BY ASPARAGINE RESIDUES OF CALCIUM PERMEABILITY AND MAGNESIUM BLOCKADE IN THE NMDA RECEPTOR. SCIENCE , 257 (5075) 1415 - 1419.

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Abstract

The N-methyl-D-aspartate (NMDA) receptor forms a cation-selective channel with a high calcium permeability and sensitivity to channel block by extracellular magnesium. These properties, which are believed to be important for the induction of long-term changes in synaptic strength, are imparted by asparagine residues in a putative channel-forming segment of the protein, transmembrane 2 (TM2). In the NR1 subunit, replacement of this asparagine by a glutamine residue decreases calcium permeability of the channel and slightly reduces magnesium block. The same substitution in NR2 subunits strongly reduces magnesium block and increases the magnesium permeability but barely affects calcium permeability. These asparagines are in a position homologous to the site in the TM2 region (Q/R site) of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors that is occupied by either glutamine (Q) or arginine (R) and that controls divalent cation permeability of the AMPA receptor channel. Hence AMPA and NMDA receptor channels contain common structural motifs in their TM2 segments that are responsible for some of their ion selectivity and conductance properties.

Type: Article
Title: CONTROL BY ASPARAGINE RESIDUES OF CALCIUM PERMEABILITY AND MAGNESIUM BLOCKADE IN THE NMDA RECEPTOR
Keywords: MOUSE CENTRAL NEURONS, SPINAL-CORD NEURONS, GLUTAMATE-ACTIVATED CHANNELS, VOLTAGE-DEPENDENT BLOCK, LONG-TERM POTENTIATION, CENTRAL-NERVOUS-SYSTEM, D-ASPARTATE RESPONSES, AMINO-ACID RECEPTORS, MOLECULAR-CLONING, DIVALENT-CATIONS
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
URI: http://discovery.ucl.ac.uk/id/eprint/127434
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