Figure 5.

Patch clamp experiments: effects of riluzole on INaP. (A) High gain recording of the sodium current evoked by a membrane voltage step from −90 to −20 mV for 250 ms, at 2 s intervals. The current peaks (INaT) are truncated by the amplifier. Currents are shown in one cell while perfused with normoxic bath solution, hypoxic bath solution and hypoxic bath solution containing vehicle (propylene glycol) equivalent to that used to solubilize 100 µM riluzole (cell capacitance = 167 pF). (B) High gain recording of the sodium current evoked as in A in a cell perfused with hypoxic bath solution with vehicle alone, or riluzole at a concentration of 0.01, 0.03, 0.1, 0.3, 1.0, 3.0 and 10 µM (traces from bottom to top, respectively, 10 µM trace labelled). The topmost trace was recorded in the presence of 20 µM TTX (labelled) (cell capacitance = 287 pF). (C) Compiled data for the block of INaP evoked as in A. Data points show mean and standard error of the mean for % block of INaP in hypoxic solution at each concentration of riluzole; numbers in brackets indicate the number of rats (n) for each data point (multiple cell recordings from a single rat were averaged and counted as one recording). The line shows the best fit of the Hill equation with the Hill coefficient fixed at 0.5: IC₅₀ was 2.7 µM (95% confidence interval 1.0 to 7.1 µM). [note that 100 µM (75% block) was the limit of solubility of riluzole, so a maximum block could not be determined].