(A) Representative current traces evoked by the indicated voltage protocol in transfected HEK293 cells. For each channel the potential resulting in maximal inward current is colored green. (B) Voltage-dependence of steady-state SI shows a −41.9 mV shift of V1/2 for Nav1.7/ΔL955 (blue squares, n = 6) to more hyperpolarized potentials and a 16.2 mV shift for Nav1.7/V948C (crossed red squares, n = 6) to more depolarized potentials compared to WT (filled black squares, V1/2 = −63.5 ± 2.1 mV, n = 10). (C) Normalized conductance–voltage relationships show a −17.7 mV shift of V1/2 for Nav1.7/ΔL955 (blue squares, n = 7) to more hyperpolarized potentials and a +8.1 mV shift of V1/2 for Nav1.7/V948C (crossed red squares, n = 7) to more depolarized potentials compared to WT (filled black squares, V1/2 = −26.8 ± 1.6 mV, n = 6). (D) The IEM mutant Nav1.7/ΔL955 shows increased relative persistent currents (n = 14, blue squares) compared to Nav1.7/V948C (crossed red squares, n = 10) and Nav1.7 WT (filled black squares, n = 19). Data shown in (D) were recorded in the presence of β4-peptide and 50 nM ATX-II and were significantly different for WT and Nav1.7/ΔL955 (blue*), and for Nav1.7/ΔL955 and Nav1.7/V948C (black#), p < 0.05. (E) V1/2 of steady-state fast inactivation is not altered by Nav1.7/ΔL955 (blue squares, n = 7) whereas Nav1.7/V948C (crossed red squares, n = 7) shifts V1/2 by −7.8 mV to more hyperpolarized potentials compared to WT (filled black squares, V1/2 = −81.4 ± 1.9 mV, n = 6).