Increasing internodal distance in myelinated nerves accelerates nerve conduction to a flat maximum

Predictions that conduction velocities are sensitive to the distance between nodes of Ranvier in myelinated axons have implications for nervous system function during growth and repair. Internodal lengths defined by Schwann cells in hindlimb nerves, for example, can undergo a 4-fold increase during mouse development, and regenerated nerves have internodes that are uniformly short. Nevertheless, the influence of internodal length on conduction speed has limited experimental support. Here, we examined this problem in mice expressing a mutant version of periaxin, a protein required for Schwann cell elongation. Importantly, elongation of mutant Schwann cells was retarded without significant derangements to myelination or axon caliber. In young mice with short mutant Schwann cells, nerve conduction velocity was reduced and motor function was impaired. This demonstrates a functional relationship between internodal distance and conduction speed. Moreover, as internodes lengthened during postnatal growth, conduction velocities recovered to normal values and mutant mice exhibited normal motor and sensory behavior. This restoration of function confirms a further prediction by Huxley and Stämpfli that conduction speeds should increase as internodal distances lengthen until a "flat maximum" is reached, beyond which no further gains in conduction velocity accrue.