Relation of agonist potency, ion channel gating and substituent molecular volume to EtOH sensitivity in NMDA receptors containing NR2A(F637) mutant subunits. Graphs plot log IC50 for EtOH vs log EC50 values for glutamate peak and steady-state current (a) maximal Iss:Ip for glutamate (b), mean open time (c) and substituent molecular volume in Å3 (d) for the various substituents at NR2A(F637). Data points are labeled with the substituted amino acid for the various mutants at NR2A(F637). The lines shown are the least squares fits to the data. Highly significant correlations were obtained between log EtOH IC50 and log EC50 for glutamate activation of peak (R2=0.626, P<0.001) and steady-state (R2=0.743, P<0.0001) current, but not glutamate maximal Iss:Ip (R2=0.001, P>0.05) or mean open time (R2=0.006, P>0.05). A significant linear relation was obtained between log EtOH IC50 and molecular volume (R2=0.587; P<0.005), but not hydropathy (R2=0.001, P>0.05), polarity (R2=0.003, P>0.05) or hydrophilicity (R2=0.276, P>0.05).