While the postnatal length growth of the largest internodes in the rat sural nerve (SN) is proportional to nerve elongation, in the developing inferior alveolar nerve (IAN), early postnatal myelin sheath remodelling allows internodal lengthening to exceed the growth rate of the whole nerve. To assess the functional consequences of ongoing myelin sheath remodelling in a developing nerve, we examined the physiological properties of the mental nerve (MN), a cutaneous IAN branch and the SN during maturation. In addition, the nodal spacing and the microscopic anatomy of the nodes in the two nerves were studied. The youngest MNs and SNs (2 weeks) exhibited comparable sensitivities to K(+)-channel blockade with 4-aminopyridine (4-AP), although myelin sheath remodelling was more frequent in the MNs. Subsequently, myelin sheath remodelling ceased in both nerves but the MNs exhibited a greater sensitivity to 4-AP. Large fibers in adult MNs and SNs had a similar nodal anatomy but the former had shorter internodes. Thus, myelin sheath remodeling, per se, does not appear to be a determinant of 4-AP sensitivity in mammalian myelinated fibers. Rather, sensitivity to potassium channel blockade is more likely mediated at the internodal or molecular level.