Alterations in the ultrastructure of peripheral nodes of Ranvier associated with repetitive action potential propagation.

We have studied the structure of the node of Ranvier following physiological activation and electrophysiological monitoring. Our results indicate that some structures within the nodal complex undergo microanatomic alterations concomitant with repetitive impulse propagation. The experiments were designed to determine the nature and extent of the morphologic changes and any associated changes in the compound action potential. Frog dorsal roots were examined by thin-section electron microscopy after having been either implanted, but not stimulated ("0 Hz control"), or orthodromically activated for 15 min at frequencies of 2, 5, 20, or 50 Hz. Roots were either fixed immediately and processed for electron microscopy or were allowed to recover for periods of 15, 30, or 45 min prior to fixation. A change in nodal structure was found that correlates with the different stimulation regimens. Specifically, there was an increase in the size and number of (extracellular) paranodal intramyelinic vacuoles after stimulation at 20 or 50 Hz when compared both to the implanted nonstimulated controls and to fibers stimulated at low frequency (2 or 5 Hz). This morphologic change occurs in the vicinity of the nodal complex without similar alterations in the morphology of the internodal regions or changes in the dimensions of the nodal gap. This form of microanatomic changes is reversible and is not seen if stimulation is halted and the fiber bundle allowed to recover in Ringer's prior to processing for morphologic evaluation. Changes in the compound action potential (CAP) parallel this structural alteration. The CAP is seen to slow and decrease in amplitude through the 15 min stimulation phase and then to regain its velocity and amplitude during the recovery. When TTX was applied to the preparation during stimulation the CAP was abolished and changes in the paranodal structure were not observed. Structure-function relationships indicated by these results are discussed in the context of several dynamic aspects of nodal physiology.