PMID- 9680238
OWN - NLM
STAT- MEDLINE
DCOM- 19981001
LR  - 20200531
IS  - 0028-3908 (Print)
IS  - 0028-3908 (Linking)
VI  - 37
IP  - 2
DP  - 1998
TI  - Structural determinants of the blocker binding site in glutamate and NMDA 
      receptor channels.
PG  - 139-47
AB  - Glutamate receptor channels of the NMDA-type (N-methyl-D-aspartate) and 
      non-NMDA-type (GluR) differ in their pore properties. The N-site in the M2 
      transmembrane segment of NMDA receptors (NMDAR), or the corresponding Q/R-site in 
      GluRs, is a pivotal structural determinant of their permeation and blockade 
      characteristics. Substitutions at a second site in M2, the L-site (L577) in 
      GluR1, drastically alter the receptor selectivity to divalent cations. Here we 
      report that M2 mutants carrying an asparagine or a threonine residue at the 
      Q-site of GluR1, along with a tryptophan residue at the L-site, form homomeric 
      GluR1 channels that are highly sensitive to structurally diverse, uncompetitive 
      NMDA antagonists such as arylcyclohexylamines, dibenzocycloheptenimines, and to 
      morphinian and adamantane derivatives. Analysis of the voltage dependence of 
      channel blockade locates the blocker binding site approximately 0.65 partway into 
      the transmembrane electric field in both GluR1 mutants and NMDAR channels. Our 
      results suggest that the homomeric GluR1 double mutants, L577W/Q582N and 
      L577W/Q582T, fairly approximate the pore properties of the heteromeric NMDA 
      receptor and support the structural kinship of their permeation pathways.
FAU - Ferrer-Montiel, A V
AU  - Ferrer-Montiel AV
AD  - Department of Biology, University of California San Diego, La Jolla 92093-0366, 
      USA.
FAU - Merino, J M
AU  - Merino JM
FAU - Planells-Cases, R
AU  - Planells-Cases R
FAU - Sun, W
AU  - Sun W
FAU - Montal, M
AU  - Montal M
LA  - eng
GR  - GM-49711/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Neuropharmacology
JT  - Neuropharmacology
JID - 0236217
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (Receptors, Glutamate)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
SB  - IM
MH  - Amino Acid Substitution
MH  - Animals
MH  - Excitatory Amino Acid Antagonists/*metabolism
MH  - Mutagenesis, Site-Directed
MH  - Patch-Clamp Techniques
MH  - Receptors, Glutamate/chemistry/*metabolism
MH  - Receptors, N-Methyl-D-Aspartate/chemistry/*metabolism
MH  - Xenopus
EDAT- 1998/07/29 00:00
MHDA- 1998/07/29 00:01
CRDT- 1998/07/29 00:00
PHST- 1998/07/29 00:00 [pubmed]
PHST- 1998/07/29 00:01 [medline]
PHST- 1998/07/29 00:00 [entrez]
AID - S0028390898000070 [pii]
AID - 10.1016/s0028-3908(98)00007-0 [doi]
PST - ppublish
SO  - Neuropharmacology. 1998;37(2):139-47. doi: 10.1016/s0028-3908(98)00007-0.