Fig. 6

Navβ4 C-terminus is important for positive regulation of resurgent currents. a Illustration of Navβ4 subunit, which consists of an extracellular immunoglobulin-like domain, a single transmembrane domain, and a cytoplasmic tail. The cytoplasmic tail contains the β4 peptide sequence (amino acids 183–203) proposed to mediate resurgent currents. Inset highlights the 20 amino acids segment sequence of the cytoplasmic tail of Na_Vβ4 corresponding to residues 183–203 of the rat protein. Red lettering indicates five lysine residues corresponding to Navβ4-WT (Β4-WT) sequence in C-terminal region that were neutralized to alanine to generate a predicted inactive form of Navβ4 (Navβ4-Mt). b Representative trace obtained from transfected DRG neurons with Nav1.6r and Navβ4-Mt. Navβ4-Mt peak resurgent current is highlighted in purple. For comparison representative trace of peak resurgent current obtained from Navβ4-WT group is highlighted in blue and control is highlighted in black. c Overexpression of Navβ4-Mt significantly decreased the percentage of DRG neurons that generated resurgent current compared to Navβ4-WT (p < 0.0001, χ² test) but not significantly different to control. d Resurgent current amplitude in Navβ4-Mt group (purple circles, n = 16) was significantly decreased compared to Navβ4-WT (blue line) but not different to control. Note that resurgent currents were normalized to peak transient currents and plotted as a function of voltage. Navβ4-WT and control data is plotted as a line of the average for reference. Navβ4-Mt summary data are mean ± SEM