Sustained increase in the excitability of myelinated peripheral axons to depolarizing current is mediated by Nav1.6

► Threshold tracking protocols show abnormal excitability in axons of Scn8amed mice. ► Changes in axonal excitability during subthreshold depolarization are strongly reduced. ► Nav1.6 has a specific function in axonal threshold electrotonus responses. ► Nav1.6 underlies persistent sodium current in peripheral myelinated axons.