Nodes of Ranvier in acrylamide neuropathy: voltage clamp and electron microscopic analysis of rat sciatic nerve fibres at proximal levels.

Adult male rats were injected with acrylamide monomer (50 mg/kg i.p., 3 times/week). The animals developed hind limb paresis and distal motor nerve conduction velocity decreased. Three of 14 examined isolated myelinated sciatic nerve fibres showed a reduced excitability. In the remaining fibres the action potentials were normal. Potential clamp analysis of nodes of Ranvier in the single fibres revealed large delayed nodal K currents in 6 cases. Four of these 6 fibres exhibited a markedly increased membrane capacitance and in 2 fibres an increased Na permeability was found. Electron microscopic examination of sciatic nerves revealed comparatively subtle internodal and nodal-paranodal alterations in large myelinated fibres. Internodally, focal aggregates of tubulovesicular profiles could be found and some Schwann cells were hypertrophic. Paranodally, axonal evaginations penetrated in between the terminating myelin lamellae. Some paranodes had a very thin myelin covering and/or exhibited varying degrees of myelin sheath retraction. In the nodal axon domains lacking an axolemmal undercoating and partly non-undercoated axolemmal protrusions could be found. Similar physiological and morphological alterations occur in the rat sciatic nerve above a neuroma. Therefore, the presently observed proximal changes may, to some extent, represent non-specific alterations, secondary to a target deprivation caused by the distal axon degeneration typical for acrylamide neuropathy.