Mechanisms of hyperpolarization in regenerated mature motor axons in cat

Abstract

We found persistent abnormalities in the recovery of membrane excitability in long-term regenerated motor nerve fibres in the cat as indicated in the companion paper. These abnormalities could partly be explained by membrane hyperpolarization. To further investigate this possibility, we compared the changes in excitability in control nerves and long-term regenerated cat nerves (3-5 years after tibial nerve crush) during manoeuvres known to alter axonal membrane Na + -K + pump function: polarization, cooling to 20• C, reperfusion after 10 min ischaemia, and up to 60 s of repetitive stimulation at 200 Hz. The abnormalities in excitability of regenerated nerves were reduced by depolarization and cooling and increased by hyperpolarization and during postischaemia. Moreover, the time course of recovery of excitability from repetitive stimulation and ischaemia was prolonged in regenerated nerves. Our data are consistent with an increased demand for electrogenic Na + -K + pumping in regenerated nerves leading to membrane hyperpolarization. Such persistent hyperpolarization may influence the ability of the axon to compensate for changes in membrane potential following normal repetitive activity.

Sensory axonal dysfunction in cervical radiculopathy

“…These results fit the ‘fanning-out’ profile, which was described by Kaji17 in 1997. These results are similar to those reported for hyperpolarised axons,18 and suggest that the sensory axons may be hyperpolarised due to proximal nerve compression.…”

Evaluation of Na+/K+ pump function following repetitive activity in mouse peripheral nerve

“…2A) and H40 (Fig. 2B) to detect changes in membrane potential, by applying additional continuous external polarization as previously described in cat nerves (Moldovan and Krarup, 2004a). We found that, in agreement with previous studies , hyperpolarziation increased the deviation of both D10 and H40 ("fanning out") and depolarization had opposite effects (Fig.…”

“…During TE, changes in accommodation were shown to be an excitability measure very sensitive to changes in membrane potential, in both human and animal (Moldovan and Krarup, 2004a) studies. It is however, not feasible to monitor a full 100 ms threshold electrotonus measurement "longitudinally" with the time resolution required to follow changes in excitability after repetitive stimulation (unpublished personal observations).…”

“…The technique of "threshold tracking" was previously used to measure the changes in excitability following long stimulus trains in clinical (Burke et al, 2001) and experimental (Moldovan and Krarup, 2004a) studies using a software written in BASIC (QTRAC, © Professor H. Bostock, Institute of Neurology, University College, London). In this study we developed a new threshold tracking system as a MATLAB (Mathworks Inc.) function library.…”

“…Conventionally the "threshold" was defined as the current required to elicit a target response that is 40-50% of the maximal response (Bostock et al, 1998). Activity dependent decrease in excitability (threshold increase) was found in human (Kiernan et al, 1997a(Kiernan et al, ,b, 2004 and cat nerves (Moldovan and Krarup, 2004a). These studies, however, offered only limited possibility to combine threshold tracking with pharmacologic or genetic manipulations.…”