Fig. 4

a–c Light-induced inhibition of hNa_V1.6 current by photolysis of 100 nM HwTxIV-Nvoc. Note that not all of the HwTxIV-Nvoc is uncaged by photolysis during this exposure time. a Representative recordings of hNa_V1.6 current with caged HwTxIV (orange) and after various illumination times (purple) and (b) average normalized time courses of hNa_V1.6 current inhibition during and following light application (n = 11, mean ± SEM). Scale: 2 ms, 1 nA. c Average normalized current at steady-state in control (dark), caged (orange) and uncaged (purple) conditions (n = 11, ***p < 0.001, two-sided repeated-measures 1-way ANOVA followed by Bonferroni’s post-test.). d Representative recordings of hNa_V1.2 current with caged HwTxIV (orange) and after illumination (purple). Scale: 2 ms, 1 nA. e Average normalized current at steady-state in control (dark), caged (orange), and uncaged (purple) conditions (n = 12, mean ± SEM ***p < 0.001, two-sided repeated-measures 1-way ANOVA followed by Bonferroni’s post-test). f–g Controllable uncaging of HwTxIV-Nvoc via UV irradiation. f Left: Superimposition of normalized hNa_V1.6 currents at steady-state recorded after varying durations of illumination. Middle: Average normalized time courses of hNa_V1.6 current inhibition (n = 40 cells, mean ± SEM). Arrow indicates steady-state. Right: Plot of current amplitude at the end of 800 s recording versus duration of illumination at 365 nm. Scale: 2 ms, 20% of amplitude. g Left: Superimposition of normalized hNa_v1.6 currents at steady-state recorded after varying power of illumination (4 min). Middle: Average normalized time courses of hNa_v1.6 current inhibition (n = 43 cells, mean ± SEM). Arrow indicates steady-state. Right: Plot of current amplitude at the end of 800 s recordings versus duration of illumination at 365 nm. Scale: 2 ms, 20% of amplitude. h Representative examples of photocontrol (365 nm, 45 mW/cm²) of 1 nM AaHII-R⁶²K-Nvoc activity on hNa_V1.2 current (left, AaHII PDB code 6NT4⁸), 100 nM BeKm1-Nvoc activity on hERG current (middle, BeKm-1 PDB code 1J5J⁴⁰) and 100 nM charybdotoxin-Nvoc activity on K_V1.2 current (right, ChTx PDB code 4JTA⁴¹). AaHII-R⁶²K toxin induces slowing of inactivation of hNa_V1.2, while BeKm1 and charybdotoxin induce block of hERG and K_V1.2 channels, respectively. For AaHII-R⁶²K-Nvoc and BeKm1-Nvoc, scale is 2 ms and 1 nA. For charybdotoxin-Nvoc, scale is 400 ms and 200 pA. Source data are provided as a Source Data File.