Nodes of Ranvier above a neuroma in the rat sciatic nerve: voltage clamp analysis and electron microscopy

Neuroma formation was induced in adult rat sciatic nerves and the animals were allowed to survive for 1-10 months. In 10 animals single large myelinated fibres from the nerve segment above the neuroma were subjected to voltage clamp analysis. Six animals were fixed by glutaraldehyde perfusion and nodes of Ranvier or large myelinated fibres above the neuroma were examined in the electron microscope (EM). Most fibres exhibited normal action potentials, but a few had a reduced excitability and small action potentials. Some fibres had increased membrane time constant and leak conductance and a markedly increased membrane capacitance. Most of the examined nodes of Ranvier exhibited abnormally large delayed K currents, which could be blocked with 4-aminopyridine (4-AP). The Na current was normal. In the EM most large cross-cut myelinated axons were markedly atrophic, particularly after long survival times. Evaginations from the paranodal region of these axons penetrated between the terminating paranodal myelin lamellae. The nodal axolemmal undercoating could be very prominent and in some cases the nodal axon was irregular. These findings show that large myelinated peripheral nerve fibres, which are chronically disconnected from their peripheral targets, exhibit specific structural and functional abnormalities of the nodes of Ranvier.