Fig. 3: Structure and characterization of the Na_X selectivity filter.

a Na_X DENA-motif side-chains shown as sticks. b Residues in Na_X that form a conserved interaction network around the selectivity filter in Na_V channels (Na_V1.7, PDB 6J8J). c Superimposed view of the DI-DIV interface comparing Na_X and Na_V1.7 (gray, PDB 6J8J). d View as in b, Na_X and Na_V1.7 selectivity filter electrostatic surface rending. Note, central cavity and activation gate excluded for clarity. e Representative currents from HEK293T cells expressing human Na_X-QTT with a C-terminal GFP-Flag tag in a physiological (left) or NMDG⁺-only extracellular solution (middle). See methods for composition of intracellular (IC) and extracellular (EC) solutions. Steps between +80 to −100 mV, in 20 mV increments, from a HP of 0 mV. Right, shows I–V curve data summary from n = 6 cells over two independent experiments. Data are shown as mean ± SD. Numbers of biological replicates (n) are indicated. f Representative currents from HEK293T cells expressing human Na_X-QTT with indicated monovalent cations in the extracellular solution. Voltage ramp from −80 to +80 mV was applied. Right, summary of reversal potentials and permeability ratios measured from three independent experiments. Data are shown as mean ± SD. Numbers of biological replicates (n) are indicated.