Mutations at NR2A(Phe-637/Met-823) can alter NMDA receptor ethanol
sensitivity. A, records are currents activated by 10
μm glutamate and 50 μm glycine and their
inhibition by 100 mm ethanol (EtOH) in cells expressing
NR1 and wild type NR2A subunits (F/M) or NR2A subunits containing
various mutations at Phe-637 and Met-823. B, concentration-response
curves for ethanol inhibition of glutamate-activated current in cells
expressing various dual site substitution mutations at NR2A(Phe-637/Met-823).
Data are means ± S.E. of 5–12 cells; error bars not visible were
smaller than the size of the symbols. Curves shown are the best fits
to the equation given under “Experimental Procedures.” The fit for
the wild type NR2A subunit is shown as a dashed line. Plots for
single-site mutations are not shown. C, average IC50
values for ethanol inhibition of glutamate-activated current in cells
expressing NR1 and wild type NR2A subunits (F/M) or NR2A subunits
containing various mutations at Phe-637 and Met-823. *, EC50 values
that are significantly different from that for wild type NR1/NR2A subunits
(**, p < 0.01; ANOVA followed by Dunnett's test). Results are
means ± S.E. of 5–12 cells. Values for wild type, NR2A(F637A),
and NR2A(F637W) are from Ref.
24; values for NR2A(M823A),
NR2A(M823F), and NR2A(M823W) are from Ref.
22.