The spatial distribution of excitability and membrane current in normal and demyelinated mammalian nerve fibres.

Thresholds to electrical stimulation have been recorded, concurrently with the membrane currents of conducted impulses, at many positions along undissected single fibres in rat spinal roots. In normal myelinated fibres, distinct threshold minima invariably coincided with sites of inward current generation, and were therefore identified as nodes of Ranvier. Between nodes, the thresholds rose by an order of magnitude. At normal nodes, the charge thresholds were linearly related to stimulus duration, as predicted by computer simulations of a model myelinated fibre (Bostock, 1983). The strength-duration time constants averaged 64.9 +/- 8.3 microseconds (mean +/- S.D.) at 37 degrees C, and had a Q10 of 1/1.39. They were relatively insensitive to changes in inter-electrode distance, or to partial anaesthetization with tetrodotoxin. In fibres treated with diphtheria toxin 6-8 days previously, to induce paranodal or segmental demyelination, threshold minima were found both at nodes and in internodal regions generating inward membrane current. In these fibres strength-duration curves were of the same general form as at normal nodes, but with strength-duration time constants increased at widened nodes (up to 350 microseconds) and at excitable internodes (600-725 microseconds). Comparison with the computer model indicated that these changes were most likely due to exposure of axon membrane with a time constant much longer than that of the normal nodal membrane. In none of the demyelinated fibres examined have we found any evidence of hyperexcitability.