Mm. Zarei et Ja. Dani, IONIC PERMEABILITY CHARACTERISTICS OF THE N-METHYL-D-ASPARTATE RECEPTOR-CHANNEL, The Journal of general physiology, 103(2), 1994, pp. 231-248
N-methyl-D-aspartate (NMDA) receptor channels in cultured CAI hippocam
pal neurons were studied using patch-clamp techniques. The purpose of
the research was to determine the occupancy of the channel by permeant
cations and to determine the influence of charged residues in or near
the pore. The concentration dependence of permeability ratios, the mo
le-fraction dependence of permeability ratios, the concentration depen
dence of the single-channel conductance, and a single-channel analysis
of Mg2+ block all independently indicated that the NMDA receptor beha
ves as a singly-occupied channel. More precisely, there is one permean
t cation at a time occupying the site or sites that are in the narrow
region of the pore directly in the permeation pathway. Permeability-ra
tio measurements in mixtures of monovalent and divalent cations indica
ted that local charges in or near the pore do not produce a large loca
l surface potential in physiologic solutions. In low ionic strength so
lutions, a local negative surface potential does influence the ionic e
nvironment near the pore, but in normal physiologic solutions the surf
ace potential appears too small to significantly influence ion permeat
ion. The results indicate that the mechanism for the high Ca2+ conduct
ance of the NMDA receptor channel is not the same as for the voltage-d
ependent Ca2+ channel (VDCC). The VDCC has two high affinity, interact
ing binding sites that provide high Ca2+ selectivity and conductance.
The binding site of the NMDA receptor is of lower affinity. Therefore,
the selectivity for Ca2+ is net as high, but the lower affinity of bi
nding provides a faster off rate so that interacting sites are not req
uired for high conductance.