Changes in excitability of human motor axons underlying post‐ischaemic fasciculations: evidence for two stable states.

Abstract

SUMMARY1. We have investigated the origin of post-ischaemic ectopic discharges in human nerve by recording changes in electrical excitability following periods of ischaemia (15-20 min) sufficient to induce spontaneous motor fasciculations. The ulnar nerve was stimulated beneath a pressure cuff on the upper arm, and compound motor action potentials recorded from abductor digiti minimi.2. On releasing the cuff after 15 min of ischaemia, thresholds to short current pulses increased in two distinct phases: a slow phase followed by a rapid rise to a peak threshold. The rapid rise was too fast to track (i.e. 100 % threshold increase in less than 4 s), and was sometimes followed after 30-40 s by an equally rapid fall. Small polarizing currents affected the timing of the rapid threshold increase, as if it was occurring at a particular membrane potential.3. By recording complete stimulus-response curves every few seconds, we found that the rapid threshold changes were associated with a bimodal distribution of thresholds. Most fibres were found in either a high-threshold or low-threshold state, and these two states converged over a period of about 10 min.4. Spontaneous motor fasciculations were only recorded after the rapid rise in threshold and when the fibres existed in two threshold states. The spontaneous activity was not responsible for inducing the two states, since they could also be recorded in its absence.5. A computer model of a human motor axon node and internode was constructed, incorporating channel types demonstrated in other axons, and channel densities adjusted to match the responses of human axons to depolarizing and hyperpolarizing current pulses. An increase in extracellular potassium concentration produced a region of negative slope conductance in the current-voltage relationship of the model, and the appearance of two stable states with enhanced activity of the electrogenic sodium pump.6. Transitions between the two stable states of the model could account qualitatively for the rapid threshold changes recorded from post-ischaemic axons. In the model, spontaneous action potentials occurred following some transitions from the high potential state to the low potential state. We suggest that postischaemic motor fasciculations in man also involve transitions between two MS 9120 H. BOSTOCK AND OTHERS equilibrium states, occurring in axons with high extracellular potassium and high electrogenic pump activity.

Influence of the skeletal muscle activity on time and frequency domain properties of the body surface ECG during evolving ventricular fibrillation in the pig

“…In our study EMG signals exhibited a very broad spectrum in the measured frequency band (2−250 Hz), which resembles muscular "fibrillation" resulting from asynchronous firing of the individual fibers of a motor unit following denervation [18,19]. Speculatively, the mechanism of SMA observed in our study may involve hyperexcitability in the motor neurons and/or skeletal muscle fibers, resulting from extracellular accumulation of potassium and depolarization of the membrane potential [20,21].…”

Excitation block in a nerve fibre model owing to potassium-dependent changes in myelin resistance

“…The effect of potassium depolarization has been modelled e.g. by Bostock et al [1,2] for the case of ischaemic conditions. The effect of the Na þ ,K þ -pump was studied in human nerves e.g.…”

Differences in Membrane Properties in Simulated Cases of Demyelinating Neuropathies: Internodal Focal Demyelinations with Conduction Block

“…We would like to remind the reader that the channel types are also in accordance with the directly investigated ion channels in human axons [22,23]. The resting potential (−86.7 mV) as an especially sensitive variable is derived from measurements on human ulnar nerve [21] and on human myelinated nerve fibres [23]. This value is more negative than those reported in rabbit (−80 mV, [24]) and rat (−80 mV, [25]; −78 mV, [26,27]).…”

“…The electrotonic potentials are simulated by adding a 100 ms subthreshold current to the center of each internodal segment and the case of periodic kind of uniform fibre polarization is also realized. The periodic kind of uniform polarization is first simulated in the human motor electrotonus model [19], since the in vivo situation for recording threshold electrotonus in man, where current is applied to the peripheral nerve via its high-resistance sheath and a 1 cm diameter surface electrode [21], is thought to correspond more closely to periodic kind of uniform polarization than point fibre polarization. The potentials are calculated for hyperpolarizing and depolarizing currents, which correspond to 0.4 times the threshold for a 1 ms current pulse.…”

“…This circuit is based on a complex extended double cable structure of nodal, paranodal and internodal segments with their corresponding ion (nodal and internodal) channels. The ion channel types and their maximal permeabilities are taken from the well-known two-component (node + internode) model of human motor axons [21]. However, that model ignores spatial gradients of potentials and currents within internodes and cannot propagate intracellular potentials.…”