Fig. 2

a i) Representative recording of hNa_V1.6 currents elicited at 10 mV from a holding potential of -100 mV illustrating the extent of current block by different concentrations of noncaged HwTxIV (black) and HwTxIV-Nvoc (orange). ii) Average dose-response curves for hNa_V1.6 current inhibition by non-caged HwTxIV (black) and HwTxIV-Nvoc (orange). The data were fitted according to a Hill equation (non-caged HwTxIV IC₅₀ = 22.4 nM (n = 5) and HwTxIV-Nvoc IC₅₀ = 6539 nM (n = 7) (292-fold reduction in IC₅₀)). Scales: 2 ms, 1 nA. Note that on hNa_v1.6, high concentrations of HwTxIV-Nvoc produce a slowing of channel inactivation due to binding on a low-affinity site absent on hNa_v1.2 (Supplementary Figure ³). b i) Representative recording of hNa_V1.1 current elicited at 10 mV from a holding potential of -100 mV illustrating the extent of current block by different concentrations of non-caged HwTxIV (black) and HwTxIV-Nvoc (orange). ii) Average dose-response curves for hNa_v1.1 current inhibition by noncaged HwTxIV (black) and HwTxIV-Nvoc (orange). The data were fitted according to a Hill equation (noncaged HwTxIV IC₅₀ = 3.60 nM (n = 12); HwTxIV-Nvoc IC₅₀ = 2794 nM (n = 8) (776-fold reduction in IC₅₀). Scales: 2 ms, 1 nA. c i) Representative recording of hNa_V1.2 current elicited at 10 mV from a holding potential of -100 mV illustrating the extent of current block by different concentrations of noncaged HwTxIV (black) and HwTxIV-Nvoc (orange). Scales: 2 ms, 1 nA. ii) Average dose-response curves for hNa_v1.2 current inhibitions by non-caged HwTxIV (black) and HwTxIV-Nvoc (orange). The data were fitted according to a Hill equation (noncaged HwTxIV IC₅₀ = 3.23 nM (n = 11); HwTxIV-Nvoc IC₅₀ = 5141 nM (n = 6) (1592-fold reduction in IC₅₀)). d i) Representative recording of hNa_V1.7 current elicited at 10 mV from a holding potential of -100 mV illustrating the extent of current block by different concentrations of non-caged HwTxIV (black) and HwTxIV-Nvoc (orange). Scales: 2 ms, 0.5 nA. ii) Average dose-response curves for hNa_v1.7 current inhibitions by non-caged HwTxIV (black) and HwTxIV-Nvoc (orange). The data were fitted according to a Hill equation (non-caged HwTxIV IC₅₀ = 15.23 nM (n = 92 cells); HwTxIV-Nvoc IC₅₀ = 4467 nM (n = 83 cells) (293-fold reduction in IC₅₀)). All data are presented as mean ± SEM. Source data are provided as a Source Data File.