Effects of missense mutations on conductance-voltage relationships and
steady-state inactivation. (A) Peak conductance-voltage
relationships for WT (open circle), R524Q (filled circle), R187W (open
diamond), and R19K (filled diamond) Na+ channels expressed
in HEK cells. No significant differences were detected between WT and
mutant channels. Number of experiments was four, and all data were
pooled. Curves are fitted to the data by using the equations given in
Materials and Methods. (B) Steady-state
voltage dependence of inactivation for WT (open circle), R524Q (filled
circle), R187W (open diamond), and R19K (filled diamond)
Na+ channels. Two different protocols were used. The
prepulses were applied from −155 to −15 mV for WT, R524Q, and R19K
mutant channels, and from −140 to −10 mV for R187W mutant channel
with 10-mV increments. The half-inactivation potential and slope
factors were estimated to be −76.9 mV and 6.7 for WT, −76.4 mV and
6.8 for R524Q, −88.6 mV and 8.7 for R187W, and −77.2 mV and 6.9 for
R19K. All data were pooled and fitted as in A.
(C) Voltage dependence of the inactivation time constant
for WT and the R187W mutant channels. Note the clear difference in
maximal rate of inactivation at the depolarized membrane potentials
between WT and the R187W mutant.