Fig. 1: Characterization of and overall structure of human Na_X.

a Representative currents from Xenopus laevis oocytes expressing human Na_X or Na_V1.7. Na_X: steps between +80 to −100 mV, in 20 mV increments from a HP of 0 mV; Na_V1.7: depolarizing steps between −80 and +65 mV, in 5 mV increments, from a HP of −100 mV. b Representative currents from oocytes expressing Na_X in response to extracellular application of indicated compounds (BDS-I Blood depressing substance I, ATX-II Neurotoxin 2). Voltage protocols as above. See Methods for concentrations of compounds tested. c Representative currents from oocytes expressing Na_X and co-expression of Na_V or Ca_V channel auxiliary-subunits, Na⁺/K⁺-ATPase subunits and synapse-associated protein 97 (SAP97), and in the presence of the indicated extracellular Na⁺ concentration. Voltage protocols as above. d Data summary of independent experiments performed as in parts a–c. Data are shown as mean ± SD; ns not significant; ****p < 0.0001; one-way ANOVA with Dunnett’s test (against Na_X). Exact p-values and statistical parameters are provided in Source Data. Numbers of biological replicates (n) are indicated. e Representative currents from murine Neuro-2a cells expressing human Na_X or Na_V1.7 in response to changes of the extracellular Na⁺ concentration (HP = −60 mV), as indicated, or voltage: depolarizing steps between −60 to +60 mV, in 10 mV increments from a HP of −100 mV. f Data summary of independent experiments performed as in parts e. Data are shown as mean ± SD; ns not significant; *p < 0.05; **p < 0.01; ****p < 0.0001; one-way ANOVA with Dunnett’s test (against mock-transfected cells). Exact p-values and statistical parameters are provided in Source Data. Numbers of biological replicates (n) are indicated. g Western blots of total lysate and surface fraction of proteins extracted from Neuro-2a cells probed for the indicated proteins. Data represent three independent biological replicates. h Side and extracellular view of the β3-Na_X channel complex. Approximate membrane boundaries are indicated. DI, DII, DIII, and DIV are colored in green, blue, orange, and pink, respectively, with the β3-subunit in gray surface representation.