3.1 Fast recovery in the presence of the drug.
Results of the RFI experiment in control and in the presence of
100 µM riluzole are illustrated in Fig. 1. In general, sodium channel
inhibitor drugs are most effective at short hyperpolarizing gaps, and
their inhibitory effect gradually decreases with longer
hyperpolarizations. This is conventionally explained by the progressive
dissociation of drug molecules from resting state throughout the
hyperpolarizing period because they have lower affinity to resting than
to inactivated state. In the absence of any drug, at -130 mV channels
recovered with a time constant of 0.39 ± 0.08 ms (exponentials on the
3rd power, see Methods). In the presence of 100 µM
riluzole recovery was delayed, it proceeded with a time constant of 2.25
± 0.004 ms (p = 0.00012, paired t-test, n = 9). Does this time constant
indeed reflect dissociation?