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

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Abstract
Thresholds to electrical stimulation were recorded, concurrently with the membrane currents of conducted impulses, at many positions along undissected single fibers in rat spinal roots. In normal myelinated fibers, 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 fiber (Bostock, 1983). The strength-duration time constants averaged 64.9 .+-. 8.3 .mu.s (mean .+-. SD) at 37.degree. C, and had a Q10 of 1/1.39. They were relatively insensitive to changes in inter-electrode distance, or to partial anesthetization with tetrodotoxin. In fibers 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 fibers 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 .mu.s) and at excitable internodes (600-725 .mu.s). 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 fibers examined was any evidence of hyperexcitability found.