Mm. Zarei et Ja. Dani, STRUCTURAL BASIS FOR EXPLAINING OPEN-CHANNEL BLOCKADE OF THE NMDA RECEPTOR, The Journal of neuroscience, 15(2), 1995, pp. 1446-1454
The open-channel structure of the N-methyl-D-aspartate (NMDA) receptor
was investigated to explain apparently conflicting interpretations ab
out ionic interactions within the pore. Patch-clamp techniques were ap
plied to tissue-cultured rat hippocampal neurons from the CA1 region.
A wide range of ammonium derivatives was studied to learn about the st
ructure of the pore from permeability and open-channel blocking charac
teristics. We conclude that the pore is asymmetric, having higher-affi
nity binding for organic cations from the outside and having a larger
external entrance. The minimum cross-sectional area of the pore is rec
tangular (approximate to 0.45 x 0.57 nm) and is the! single-occupancy
binding site(s) for small permeant cations. The narrow region extendin
g from this minimum cross section is short, and its shape underlies th
e voltage dependencies of blocking cations. While occupying the blocki
ng site, some open-channel blockers can interact with permeant cations
at their binding site in the minimum cross section. A structurally ba
sed hypothesis is presented, explaining that the electrostatic interac
tions between the blocking site and permeant-ion site produce a high v
olta!ae dependence for blockade by some cations.