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?