Biomedical subjects

H Bostock

Publications and source records attributed to H Bostock.

At least 37 records · Page 2Linked to original sources

PubMed2000

Effects of membrane polarization and ischaemia on the excitability properties of human motor axons.

Multiple nerve excitability measurements have been proposed for clinical testing of nerve function, since excitability measures can provide evidence of altered axonal membrane properties and are complementary to conventional nerve conduction studies. An important determinant of excitability is membrane potential, and this study was undertaken to determine the changes in a range of excitability properties associated with alterations in membrane potential. Membrane potential was varied directly using DC polarizing currents and indirectly by ischaemia. The median nerve was stimulated at the wrist and the resultant compound muscle action potentials recorded from abductor pollicis brevis. Stimulus-response behaviour, strength-duration time constant (tau(SD)), threshold electrotonus to 100-ms polarizing currents, a current-threshold relationship and the recovery of excitability following supramaximal activation were each followed in four normal subjects during the two manoeuvres, using a recently described protocol. Membrane depolarization and ischaemia produced an increase in axonal excitability, an increase in the slope of the current-threshold relationship, a 'fanning in' of responses during threshold electrotonus, a decrease in super-excitability, and increases in both tau(SD) and the refractory period. Changes in the opposite direction occurred with membrane hyperpolarization and during the post-ischaemic period. One excitability parameter differentiated between the direct and indirect changes in membrane potential: late subexcitability was sensitive to polarizing currents but relatively insensitive to ischaemia, probably because of compensatory changes in extracellular potassium ions. These results should enable multiple excitability measurements to be used as a tool to identify changes in axonal membrane potential in neuropathy.

Action Potentials↗

PubMed2000

Activity-dependent conduction block in multifocal motor neuropathy.

Patients with multifocal motor neuropathy may complain of muscle fatigue, even though the degree of conduction block assessed at rest has improved with treatment. To explore the mechanism involved, we examined changes in muscle force during maximum voluntary contraction (MVC) and monitored conduction block before and after MVC in five patients with multifocal motor neuropathy. The results were compared with those for the contralateral unaffected homonymous muscles. For one patient, who had bilateral involvement, a normal subject of a similar age and stature served as the control. Results of conduction studies were also compared with those from six patients with amyotrophic lateral sclerosis (ALS) with similar compound muscle action potential (CMAP) amplitudes after proximal stimulation. During MVC for 60 s, the affected muscles developed prominent fatigue; the force at the end of contraction compared with the initial force was significantly lower for the affected muscles [42 +/- 19% (mean +/- standard deviation) of the initial force] than for the control muscles (94 +/- 9%; P = 0.01). After MVC, the amplitude ratio of CMAPs after proximal versus distal nerve stimulation transiently decreased to 19 +/- 14% of that before MVC in the affected muscles, but not in the control muscles (94 +/- 3.8% of that before MVC) and in patients with ALS (95 +/- 6.7%). In one patient with a focal lesion in the forearm, nerve excitability was monitored at the lesion site before and after MVC for 120 s. There were significant increases in axonal threshold (approximately 48%) and supernormality (approximately 135%) immediately after MVC, suggesting that the axonal membrane had undergone hyperpolarization and, by extrapolation, that this had precipitated the conduction block. This study is the first to show that activity-dependent conduction block plays a role in human disease by causing muscle fatigue.

Action Potentials↗

PubMed1999

Human axons contain at least five types of voltage-dependent potassium channel.

1. We investigated voltage-gated potassium channels in human peripheral myelinated axons; apart from the I, S and F channels already described in amphibian and rat axons, we identified at least two other channel types. 2. The I channel activated between -70 and -40 mV, and inactivated very slowly (time constant 13.1 s at -40 mV). It had two gating modes: the dominant ('noisy') mode had a conductance of 30 pS (inward current, symmetrical 155 mM K+) and a deactivation time constant (tau) of 25 ms (-80 mV); it accounted for most ( approximately 50-75 %) of the macroscopic K+ current in large patches. The secondary ('flickery') gating mode had a conductance of 22 pS, and showed bi-exponential deactivation (tau = 16 and 102 ms -80 11 mV); it contributed part of the slow macroscopic K+ current. 3. The I channel current was blocked by 1 microM alpha-dendrotoxin (DTX); we also observed two other DTX-sensitive K+ channel types (40 pS and 25 pS). The S and F channels were not blocked by 1 microM DTX. 4. The conductance of the S channel was 7-10 pS, and it activated at slightly more negative potentials than the I channel; its deactivation was slow (tau = 41.7 ms at -100 mV). It contributed a second component of the slow macroscopic K+ current. 5. The F channel had a conductance of 50 pS; it activated at potentials between -40 and +40 V, deactivated very rapidly (tau = 1.4 ms at -100 mV), and inactivated rapidly (tau = 62 ms at +80 mV). It accounted for the fast-deactivating macroscopic K+ current and partly for fast K+ current inactivation. 6. We conclude that human and rat axonal K+ channels are closely similar, but that the correspondence between K+ channel types and the macroscopic currents usually attributed to them is only partial. At least five channel types exist, and their characteristics overlap to a considerable extent.

Adolescent↗

PubMed1999

Activity-dependent slowing of conduction differentiates functional subtypes of C fibres innervating human skin.

1. The effects of impulse activity on conduction in cutaneous C fibres have been examined in 46 microneurographic recordings from 11 normal subjects and 11 diabetic patients with normal nerve conduction. A tungsten microelectrode was inserted into a cutaneous nerve, usually the superficial peroneal close to the ankle, and intraneural microstimulation was used to identify an area of skin innervated. Three minute trains of 0.25 ms stimuli at 1, 2 and 4 Hz were then delivered to the surface of the skin, separated by intervals of 6 min with stimulation at 0.25 Hz. Slowing and block of conduction were measured from the nerve responses for up to seven C units per stimulation sequence. 2. Three types of C unit were distinguished by their responses to repetitive stimulation: type 1 units slowed progressively during the 3 min trains; slowing of type 2 units reached a plateau within 1 min; while type 3 units hardly slowed at all. Data from normal and diabetic subjects did not differ and were pooled. After 3 min at 2 Hz, the percentage increases in latency were for type 1, 28.3 +/- 9.7 (n = 63 units, mean +/- s.d.); for type 2, 5.2 +/- 1.6 (n = 14); and for type 3, 0.8 +/- 0.5 (n = 5), with no overlap. After 3 min at 4 Hz, 58 % of type 1 units (but no type 2 or 3 units) blocked intermittently. Recovery of latency after stimulation was faster for type 2 than for type 1 units, but conduction velocities of the three types were similar. 3. Type 1 units were identified as nociceptors and 7 type 2 units were identified as 'cold' fibres, activated by non-noxious cold, with no overlap in modality. None of the units tested was activated by weak mechanical stimuli or reflex sympathetic activation. 4. Spike waveforms were averaged for 18 type 1, 10 type 2 and 6 type 3 units. All units had predominantly triphasic action potentials with a major negative peak, but those of type 3 units were on average both smaller and briefer than those of type 1 and type 2 units. 5. It is concluded that repetitive electrical stimulation reliably differentiates nociceptive from cold-specific C fibres innervating human hairy skin, as has previously been shown for the rat. Cold fibres can propagate impulses continuously at much higher rates than nociceptive fibres. The nature of the type 3 units is unclear.

Adult↗

PubMed1999

Characterisation of paired-pulse transcranial magnetic stimulation conditions yielding intracortical inhibition or I-wave facilitation using a threshold-hunting paradigm.

Short-interval, paired-pulse transcranial magnetic stimulation (TMS) is usually used to demonstrate intracortical inhibition. It was shown recently that with short-interval, paired-pulse TMS a facilitation - called intracortical I-wave facilitation - can also be demonstrated. It was the aim of this study to investigate which stimulus conditions lead to intracortical inhibition and what conditions yield an intracortical I-wave facilitation in a hand muscle of normal subjects. Paired-pulse TMS responses with an interstimulus interval of 1.2 ms were obtained from the abductor digiti minimi muscle of four normal subjects. A threshold-hunting paradigm with hunting through first or second stimulus variation was used to obtain a curve of threshold-pair strengths. All subjects showed two branches of stimulus interaction on this diagram. If the first stimulus of a threshold pair was below approximately 65% of resting motor threshold it modified the response primarily due to the second stimulus through intracortical inhibition. However, if the first stimulus of a threshold pair exceeded approximately 65% of resting motor threshold it became responsible for the spinal action-potential initiation. The subsequent second stimulus served as a "booster" for the ongoing intracortical I-wave activity, making it impossible to observe the intracortical inhibition evoked by the first stimulus.

Action Potentials↗

PubMed1999

The pH dependence of late sodium current in large sensory neurons.

The effects of altering extracellular pH on late Na+ currents were investigated in large dorsal root ganglion neurons from rats (100-300 g), using patch-clamp techniques. The late current amplitude was steeply dependent upon pH over a range which included normal physiological values: raising the pH from 7.3 to 8.3 approximately doubled the amplitude. Whole-cell late currents 60 ms after depolarization to - 30 mV were blocked with an apparent pKa of 6.96. The pH-dependent changes in current amplitude could not be accounted for by the effects of altered surface charge. In recordings of unitary Na+ currents from outside-out membrane patches, acidification promoted channel opening to a reduced conductance level, near one-half of its maximal value. Acidification to pH < 6.0 also changed the kinetics of the current recruited with the lowest threshold from non-inactivating to inactivating, with the elimination of late openings. We conclude that lowering pH from an initial alkaline or neutral value blocks late Na+ current by reducing the number of contributing channels while also reducing the single channel conductance. The pH dependence of late Na+ current helps to explain clinically relevant changes in neuronal excitability in response to small (i.e. < 1 unit) perturbations in extracellular pH.

Animals↗

PubMed1998

Threshold tracking techniques in the study of human peripheral nerve.

Conventional electrophysiological tests of nerve function focus on the number of conducting fibers and their conduction velocity. These tests are sensitive to the integrity of the myelin sheath, but provide little information about the axonal membrane. Threshold tracking techniques, in contrast, test nerve excitability, which depends on the membrane properties of the axons at the site of stimulation. These methods are sensitive to membrane potential, and to changes in membrane potential caused by activation of ion channels and electrogenic ion pumps, including those under the myelin sheath. This review describes the range of threshold tracking techniques that have been developed for the study of human nerves in vivo: resting threshold is compared with the threshold altered by a change in environment (e.g., ischemia), by a preceding single impulse (e.g., refractoriness, superexcitability) or impulse train, or by a subthreshold current (e.g., threshold electrotonus). Few clinical studies have been reported so far, mainly in diabetic neuropathy and motor neuron disease. Threshold measurements seem well suited for studies of metabolic and toxic neuropathies but insensitive to demyelination. Until suitable equipment becomes more widely available, their full potential is unlikely to be realized.

Animals↗

PubMed1998

Ischemic resistance of cutaneous afferents and motor axons in patients with amyotrophic lateral sclerosis.

Compared with control subjects, patients with amyotrophic lateral sclerosis (ALS) have been reported to experience less or no paresthesias during and after release of ischemic compression of the upper arm for 10 min. This is reminiscent of the resistance to ischemia of diabetic patients, in whom sensory and motor axons undergo less ischemic depolarization and less postischemic hyperpolarization than in control subjects. The present study compared the changes in axonal excitability produced by ischemia for 10 min in 21 patients with ALS and 14 age-matched control subjects. Fewer patients reported intraischemic or postischemic paresthesias and the intensity of paresthesias was less, but this was significant only for postischemic paresthesias. There were quantitatively similar changes in refractoriness, supernormality, and strength-duration time constant during ischemic compression, but the increase in excitability of motor axons was less during the second half of ischemia in the patients. After release of ischemia the postischemic hyperpolarization was greater in the ALS patients, the opposite of what occurs in diabetes. These changes could reflect reduced intraneural K+ accumulation due to loss of motor axons or an alteration in nerve metabolism or membrane properties. Either way, the present study has failed to confirm previous reports of "ischemic resistance" in ALS, and indicates that the changes in axonal properties in ALS are not analogous to those in diabetes mellitus.

Adult↗

PubMed1998

Strength-duration properties of sensory and motor axons in amyotrophic lateral sclerosis.

In normal subjects, the strength-duration time constant is longer for cutaneous afferents than for motor axons, probably because the former express a greater non-inactivating (persistent) Na+ conductance that is active at threshold. Using a threshold-tracking system the strength-duration properties of cutaneous afferents and motor axons were recorded from 23 patients with amyotrophic lateral sclerosis, and compared with those of 32 healthy subjects. In control subjects and patients, the strength-duration time constant of sensory fibres declined with age, and there was no difference between the two groups when age was taken into account. The motor time constant did not change with age when expressed as a percentage of the time constant for sensory fibres in the same nerve, but was significantly longer for the patients than control subjects. In addition, motor rheobase was significantly lower for the patients, when expressed as a percentage of sensory rheobase. There was an inverse relationship between the time constant and rheobase for sensory and motor axons, and this was the same for the patients and the control subjects, suggesting that the variations in time constant within and between the groups were related to the expression of a common factor. Measurements of refractoriness and supernormality provided no evidence for a difference in resting membrane potential between the patients and control subjects. These findings are consistent with the interpretation that motor axons of the patients with amyotrophic lateral sclerosis have a greater persistent Na+ conductance than normal motor axons. This could contribute to the ectopic activity responsible for fasciculation.

Adult↗

PubMed1998

Modulation of voltage-activated calcium currents by mechanical stimulation in rat sensory neurons.

We examined the effects of mechanical stress, induced by a stream of bath solution, on evoked action potentials, electrical excitability, and Ca2+ currents in rat dorsal root ganglion neurons in culture with the use of the whole cell patch-clamp technique. Action-potential duration was altered reversibly by flow in 39% of the 51 neurons tested, but membrane potential and excitability were unaffected. The flow-induced increases and decreases in action-potential duration were consistent with the different effects of flow on two types of Ca2+ channel, determined by voltage-clamp recordings of Ba2+ currents. Current through omega-conotoxin-sensitive (N-type) Ca2+ channels increased by an estimated 74% with flow, corresponding to 23% increase in the total high voltage-activated current, whereas current through low-threshold voltage-activated (T-type) channels decreased by 14%. We conclude that modulation of voltage-activated Ca2+ currents constitutes a route by which mechanical events can regulate Ca2+ influx in sensory neurons.

Action Potentials↗

PubMed1998

Inactivation of macroscopic late Na+ current and characteristics of unitary late Na+ currents in sensory neurons.

Na+ currents in adult rat large dorsal root ganglion neurons were recorded during long duration voltage-clamp steps by patch clamping whole cells and outside-out membrane patches. Na+ current present >60 ms after the onset of a depolarizing pulse (late Na+ current) underwent partial inactivation; it behaved as the sum of three kinetically distinct components, each of which was blocked by nanomolar concentrations of tetrodotoxin. Inactivation of one component (late-1) of the whole cell current reached equilibrium during the first 60 ms; repolarizing to -40 or -50 mV from potentials of -30 mV or more positive gave rise to a characteristic increase in current (tau >/= 5 ms), attributed to removal of inactivation. A second component (late-2) underwent slower inactivation (tau > 80 ms) at potentials more positive than -80 mV, and steady-state inactivation appeared complete at -30 mV. In small membrane patches, bursts of brief openings (gamma = 13-18 pS) were usually recorded. The distribution of burst durations indicated that two populations of channel were present with inactivation rates corresponding to late-1 and late-2 macroscopic currents. The persistent Na+ current in the whole cell that extended to potentials more positive than -30 mV appeared to correspond to sporadic, brief openings that were recorded in patches (mean open time approximately 0.1 ms) over a wide potential range. None of the three types of gating described corresponded to activation/inactivation gating overlap of fast transient currents.

Animals↗

PubMed1997

Latent addition in motor and sensory fibres of human peripheral nerve.

1. The time constants of motor and sensory nerve fibres were studied in normal human ulnar nerves by the method of latent addition, using threshold tracking to follow the recovery of excitability after brief conditioning current pulses. The 60 microseconds test and conditioning stimuli were applied at the wrist, and the conditioning stimuli were set to 90, 60, 30, -30, -60 and -90% of the control threshold current. Compound muscle action potentials were recorded from abductor digiti minimi, and sensory nerve action potentials from the little finger. 2. Recovery from depolarizing conditioning pulses was slower than recovery from hyperpolarizing pulses and strongly dependent on conditioning pulse amplitude. The voltage dependence of latent addition was attributed to subthreshold activation of sodium channels (local response). 3. Motor and sensory nerve excitability generally recovered from -90% hyperpolarizing pulses as the sum of two exponential components, although the slow component was negligible in some motor nerves. The fast component (time constant 43.3 +/- 2.0 microseconds, mean +/- S.E.M., n = 9) was similar between motor and sensory fibres in the same subject. It showed no consistent voltage dependence, and was attributed to a passive input time constant of the fibres. The slow component of recovery from hyperpolarizing pulses was greater in sensory than in motor fibres and was voltage dependent: it could be greatly increased in motor and sensory fibres by steady depolarization. It was attributed to a regenerative membrane current, active at the resting potential in sensory and at least some motor nerves. 4. The latent addition responses were compared with the computed responses of four theoretical models. Both motor and sensory responses were well fitted by a model in which a fraction of the sodium channels (less in motor than in sensory fibres) were activated at potentials 20 mV more negative than normal and at half the normal rate, and did not inactivate. 5. It is concluded that the differences in latent addition between motor and sensory fibres are primarily due to differences in non-classical, voltage-dependent ion channels, active close to the resting potential. These "threshold channels' may help to account for the longer strength-duration time constant of sensory fibres, for their lower rheobase, and for their greater tendency to fire repetitively.

Adult↗

PubMed1997

The physiological effect of anti-GM1 antibodies on saltatory conduction and transmembrane currents in single motor axons.

Anti-ganglioside (anti-GM1) antibodies have been implicated in the pathogenesis of Guillain-Barré syndrome, multifocal motor neuropathy and motor neuron diseases. It has been held that they may interfere with saltatory conduction by blocking sodium channels. We tested this hypothesis by analysing action potentials from 140 single nerve fibres in 22 rat ventral roots using external longitudinal current measurement. High-titre anti-GM1 sera from Guillain-Barré syndrome or multifocal motor neuropathy patients, or anti-GM1 rabbit sera were applied to the rat ventral root, where saltatory conduction in single motor fibres was serially observed for 4-12 h (mean 8.2 h). For control experiments, we also tested anti-galactocerebroside (anti-GalC) sera, which causes acute demyelinative conduction block, and tetrodotoxin (TTX), a sodium channel blocker. Conduction block was found in 82% of the fibres treated with anti-GalC sera and 100% treated with TTX, but only in 2% (one out of 44) treated with the patients' sera and 5% (two out of 38) treated with rabbit anti-GM1 sera. All the nodes blocked by anti-GM1 sera revealed intense passive outward membrane current, in the internode just beyond the last active node. This pattern of current flow was similar to that in fibres blocked by demyelination with anti-GalC sera, and quite different from that seen in fibres blocked by reducing sodium currents with TTX. Our findings suggest that anti-GM1 sera neither mediate conduction block nor block sodium channels on their own. We conclude that physiological action of the antibody alone is insufficient to explain clinically observed conduction block in human diseases.

Action Potentials↗

PubMed1997

Excitability changes in human sensory and motor axons during hyperventilation and ischaemia.

This study was undertaken to compare the excitability changes of sensory and motor axons during hyperventilation and ischaemia, and to determine why ectopic impulse activity develops more readily during hyperventilation, and in sensory fibres. During hyperventilation for 20 min, all six subjects reported paraesthesiae in the hand and face, and four out of the six developed muscle twitching and cramps, associated with significant decreases of 20-30% in the threshold current required to produce sensory and motor potentials of constant size. During ischaemia four out of the six subjects reported paraesthesiae, but none reported muscle twitching. There were significant decreases of 15-20% in threshold for sensory and motor fibres. Ischaemia produced a marked decrease in supernormality, an increase in refractoriness and an increase in latency of the test compound sensory or motor potential, changes that were not seen with hyperventilation. The decrease in threshold during these manoeuvres was associated with a significant increase in strength--duration time constant (tau SD), indicating a relatively greater decrease in rheobase current. Using the technique of latent addition, we found that the changes in tau SD were consistent with a recently proposed model in which non-inactivating, voltage-dependent 'threshold channels' (presumably persistent Na+ channels) are active at resting potential. The failure of hyperventilation to alter conduction velocity, refractoriness or supernormality appreciably indicates that, unlike ischaemic depolarization, hyperventilation does not increase inactivation of conventional Na+ channels or activation of K+ channels, and this implies that the hyperventilation-induced increase in excitability is not the result of conventional depolarization, as seems to occur during ischaemia. These results suggest that hyperventilation has a rather selective action on the threshold channels, and they help to explain its greater effectiveness compared with ischaemia in provoking ectopic discharges. The greater expression of threshold channels in sensory than in motor fibres can explain why hyperventilation induces paraesthesiae before fasciculation and why only paraesthesiae occur during ischaemia.

Action Potentials↗

PubMed1997

Low-threshold, persistent sodium current in rat large dorsal root ganglion neurons in culture.

Dorsal root ganglion neurons from adult rats (> or = 200 g) were maintained in culture for between 1 and 3 days. Membrane currents generated by large neurons (50-75 microns apparent diameter) were recorded with the whole cell patch-clamp technique. Large neurons generated transient Na+ currents and at least two types of inward current that persisted throughout 200-ms voltage-clamp steps to +20 mV. One persistent current activated close to -35 mV (high threshold), whereas in about half of the cells another persistent current began to activate negative to -70 mV (low threshold). The high-threshold persistent current was identified as a Ca2+ current, as previously described in these neurons. The low-threshold current was reversibly suppressed either by replacing external Na+ with tetramethylammonium ions or by reducing external Na+ concentration ([Na+]) and simultaneously raising external [Ca2+]. It was blocked by tetrodotoxin (TTX) with an apparent equilibrium dissociation constant in the single nanomolar range. We conclude that the low-threshold current is a TTX-sensitive, persistent Na+ current. The persistent TTX-sensitive current contributed to steady-state membrane current from at least -70 mV to 0 mV, a wider potential range than predicted by activation-inactivation gating overlap for transient Na+ current. Because of its low threshold and fast activation kinetics, the persistent Na+ current is expected to play an important role in determining membrane excitability.

Animals↗

PubMed1996

Abnormal axonal inward rectification in diabetic neuropathy.

An abnormal axonal membrane conductance might contribute to human diabetic neuropathy. To test this idea, we have compared the threshold changes produced by long-lasting (100-200 ms) de- and hyperpolarizing currents applied to median motor and sensory axons at the wrist in 63 diabetic patients with those from 50 normal controls and 27 amyotrophic lateral sclerosis (ALS) patients. Averages of the threshold electrotonus plots for motor and sensory axons of diabetic patients showed more subexcitability during, and slower recovery following, the application of hyperpolarizing currents. Such alterations have been previously found in isolated rat nerves after inhibition of axonal inward rectification by means of cesium ions. The abnormalities in diabetics were positively correlated with the age of patients and the presence of neuropathy. Threshold electrotonus seen in diabetes differed strongly from the effects of acute ischemia and were unlike changes recorded in ALS. The data indicate that an abnormal inward rectification of peripheral axons is associated with diabetic neuropathy. A better understanding of the neurobiology of this conductance might provide information about the pathophysiology of this disease.

Adult↗

PubMed1996

A distributed-parameter model of the myelinated human motor nerve fibre: temporal and spatial distributions of electrotonic potentials and ionic currents.

The double cable model is used to investigate the electrotonic responses of the myelinated human motor nerve fibre to 100 ms depolarizing and hyperpolarizing current pulses. The model calculations provide estimates of the spatial and temporal distributions of the transaxonal and transmyelin components of the electrotonic potentials, both in different segments of the fibre and at different moments during and after the pulses. The temporal distributions of the potentials exhibit fast (rise time < 1 ms) and slow (from 10 to 100 ms) components, while the discontinuous spatial distributions of the potentials reflect the heterogeneous structure of the fibre. The distributions of the transaxonal and transmyelin currents along the fibre, and their contributions from different ionic channels, are also explored. The different axolemmal channel types beneath the myelin sheath make an important contribution to the responses to the long-lasting current pulses.

Action Potentials↗

PubMed1995

A distributed-parameter model of the myelinated human motor nerve fibre: temporal and spatial distributions of action potentials and ionic currents.

A double cable model of the myelinated human motor nerve fibre is presented. The model is based on the nodal and internodal channels in a previous, two-component model of human motor axons (Bostock et al. 1991), added to a complex extended cable structure of nodal, paranodal and internodal segments. The model assumes a high-resistance myelin sheath and a leakage pathway to the internodal axolemma via the paranodal seal resistance and periaxonal space. The parameter values of the model were adjusted to match the recordings of threshold electrotonus in human motor fibres from Bostock et al. (1991). Kirchoff's current law was used to derive a system of partial differential equations for the electrical equivalent circuit, and numerical integration was performed with a fixed time increment and non-uniform spatial step sizes, in accordance with the complex structure of the fibre. The model calculations provide estimates of the spatial and temporal distributions of action potentials and their transaxonal and transmyelin components, both in different segments of the fibre and at different moments during action potential propagation. The distribution of transaxonal and transmyelin currents along the fibre and their contributions from different ionic channels are also explored.

Action Potentials↗