We next examined the actions of DMCM on the GABA dose–
response relationships of the two mutants. In the case of
abL259Sg, the EC50’s were 0.07870.005 and 0.1470.004 mM
for GABA alone and GABA plus DMCM, respectively. These
values were not statistically different. While the absence of a
leftward shift with DZP was predicted, at face value it seemed
counter-intuitive that DMCM would not shift the dose–response
relationship back to the right. However, examination of the inset
in Figure 2a provides a rational explanation. Owing to the
plateau of the relationship between L and EC50 at lower values of
L, modest shifts of L in either direction would not produce a
detectable change in the EC50. We did observe a significant
rightward shift imparted by DMCM for aL263S as would be
predicted by the position of this mutant along the
L–EC50 relationship. DMCM increased the EC50 for GABA
from 0.2470.03 to 1.270.04 mM (Table 1) and this difference was
statistically significant (Po0.05). The data in Figure 2 support
the conclusion that the changes in GABA sensitivity imparted by
the TM2 mutation and DZP involve a common mechanism.