Figure 7: Different states of Na_V1.9 hyperactivity.

(a) Representative whole-cell current traces recorded at −37 mV from ND7/23 cells transiently expressing Na_V1.9 (black), Na_V1.9-V1184A (red) or Na_V1.9-L811P (blue). Fast inactivation of Na_V1.9 is not affected by mutation p.V1184A while mutation p.L811P slows down channel inactivation, thus prolonging channel opening. (b) Boltzmann functions describing the voltage dependences of opening (Γ/Γ_max) and inactivation (I₅₀₀/I₀) of wild-type Na_V1.9 (black) and mutants L811P (blue) and V1184A (red). Coloured areas indicate overlap between activation and inactivation curves, which is expected to result in a pro-excitatory window current; this window current is largest for mutation p.L811P followed by p.V1184A and wild-type Na_V1.9. (c) Current traces as shown in a were analysed to determine the fraction of channels not inactivated 80 ms after triggering channel activation with various depolarizing voltage steps. Notably, fast inactivation of mutant p.L811P (n=11) is impaired in the entire voltage range while mutation p.V1184A (n=9) does not affect fast inactivation (n=10 for Na_V1.9). Data points represent mean values with error bars indicating s.e.m. Data from Na_V1.9-L811P as in Leipold et al. (2013).