Simulation of the Sensitivity of Nerve Conduction Velocity on Internodal Length Was Performed

Supplementary Legends

Supplementary Figure 1 Composition and structure of the node and paranode regions of WT and KO peripheral nerves at 3 weeks. a, The upper panel shows a teased quadriceps nerve fibre triple-labelled with antibodies against Caspr (red), sodium channels (Nav) (green) and both neurofascin-155 and neurofascin–186 (Nfasc) (blue). The lower panel shows a fibre double-labelled for b-dystroglycan (DG) (red) and bIV-spectrin (bIV-spect) (green). The paranodal (Caspr and neurofascin-155), nodal (sodium channels, neurofascin–186 and bIV-spectrin) and microvillar (b-dystroglycan) markers were localized similarly in WT and KO Schwann cells. b, Western blot of sciatic nerve extracts (20 mg protein) showed that the amounts of bIV-spectrin and neurofascin-186 (NF186) (nodal proteins) and neurofascin-155 (NF155) and Caspr (glial and axonal paranodal proteins respectively) were higher in the KO compared to WT consistent with the approximate doubling in the number of nodes and paranodes per unit length in the KO. c, Electron micrographs of longitudinal sections of quadriceps nerves confirmed that the microvilli and paranodal axoglial junctions were intact in the KO; scale bar, 1 mm. The inset also shows intact transverse bands at the axoglial junction in both WT and KO; scale bar, 0.2 mm.

Supplementary Figure 2 Conduction velocities, internodal lengths and Cajal bands in the CMTX mouse, a late-onset demyelinating mutant. a, Conduction velocities and b, internodal lengths in quadriceps nerves from 3 week-old CMTX mice were not reduced compared to WT nerves and c, Cajal bands in CMTX sciatic nerves detected by immunofluorescence staining for S100 appeared normal.

Supplementary Figure 3 Modelling of the sensitivity of nerve conduction velocity to changes in internodal length. The model was implemented in NEURON1,2 using 10 successive internodal segments. The geometrical parameters utilised for 3 week-old mouse quadriceps nerve were: axon diameter, 3.0 mm; node diameter, 1.7 mm; paranode diameter, 1.7 mm; juxtaparanode diameter, 3.0 mm; internode diameter, 3.0 mm; juxtaparanode length, 33 mm; number of myelin lamellae, 60; internodal length, 125-1750 mm. The electrical parameters of the nerve fibre were as originally quoted1.

1. McIntyre, C. C., Richardson, A. G. & Grill, W. M. Modeling the excitability of mammalian nerve fibers: influence of afterpotentials on the recovery cycle. J Neurophysiol 87, 995-1006 (2002).

2. Hines, M. L. & Carnevale, N. T. The NEURON simulation environment. Neural Comput 9, 1179-209 (1997).