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MS 10775 Received 28 February 2000; accepted after revision 10 August 2000.
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ABSTRACT |
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INTRODUCTION |
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A previous study presented evidence that nodal slow K+ conductances are expressed less on cutaneous afferents in the sural nerve than on cutaneous afferents in the median nerve (Lin et al. 2000). The density of slow K+ channels at the node of Ranvier is some 25 times that in the internode but there is much more internodal membrane than nodal, such that the absolute number of slow K+ channels is much greater on the internodal membrane. Their kinetics are such that they probably contribute little to the repolarization after an action potential, but they can produce accommodation to maintained depolarizing stimuli and, thereby, spike-frequency adaptation (Bostock, 1995). The only method with which to examine the behaviour of internodal conductances in human subjects is threshold electrotonus (Bostock & Baker, 1988; Bostock et al. 1998), in which the threshold changes produced by prolonged subthreshold depolarizing or hyperpolarizing currents are measured. The threshold changes generally parallel the electrotonic potentials responsible for them, hence the term 'threshold electrotonus'. Because externally applied currents have a greater effect on large diameter than on small diameter axons, threshold electrotonus studies properties of primarily the larger axons in the nerve.
In threshold electrotonus studies, activation of the slow K+ conductance is probably the major factor producing accommodation to prolonged depolarizing currents (Bostock, 1995; Bostock et al. 1998). However, it is not the only internodally located conductance that can be investigated using threshold electrotonus. Inward rectification is activated by hyperpolarizing currents and acts to limit the degree of hyperpolarization, its biological role probably being to offset the activity-dependent hyperpolarization that occurs when axons conduct impulse trains (Pape, 1996). In the human median nerve, inward rectification is expressed more on sensory axons than on motor axons, such that motor axons undergo greater hyperpolarization following release of ischaemia (Bostock et al. 1994) and following repetitive activity (Vagg et al. 1998). This and other biophysical differences between sensory and motor axons can explain differences in susceptibility to conduction block in demyelinating neuropathies (Kaji et al. 2000; Cappelen-Smith et al. 2000).
The present study was undertaken using threshold electrotonus to explore whether there are differences between cutaneous afferents in the median and sural nerves in these two predominantly internodal conductances: a slow K+ conductance, responsible for accommodation to depolarizing stimuli, and inward rectification, responsible for accommodation to hyperpolarizing stimuli. The data indicate that the two nerves respond differently to prolonged subthreshold currents but that when this factor is taken into account differences still exist, suggesting that both accommodating conductances are expressed less on sural afferents than on median afferents. Accordingly, it would be expected that afferents in the upper and lower limbs respond differently to stress.
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METHODS |
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A total of 46 experiments were performed on 16 healthy volunteers (11 male, 5 female, aged 25-55 years), who gave informed written consent to the experimental procedures, which had been approved by the Committee on Experimental Procedures Involving Human Subjects of the University of New South Wales, in accordance with the Declaration of Helsinki. In each subject, identical studies were performed on the median and sural nerves. A computerized threshold-tracking program (QTRAC, Institute of Neurology, Queen Square, London, UK; see Bostock & Baker, 1988; Bostock et al. 1998) was used to adjust the intensity of the test stimuli to produce a compound sensory action potential (CSAP) that was 50 % of the maximum. The excitability of cutaneous afferents in the two nerves was changed using long-lasting subthreshold depolarizing or hyperpolarizing currents and the changes in threshold for the test CSAP were measured before, during and after the conditioning currents.
The median and sural nerves were stimulated using surface electrodes (Red-Dot, 3M Canada, Ontario, Canada), with the cathode over the nerve at the wrist or at the back of the calf, respectively, and a remote anode secured over muscle some 10-20 cm proximal to the cathode. The antidromic CSAP was recorded using ring electrodes around the index finger for the median nerve and immediately below the ankle for the sural nerve, using an interelectrode distance of 4 cm. The amplitude of the CSAP was measured from negative peak to positive peak. Skin temperature was measured at the stimulation site and between the stimulating and recording electrodes and remained constant throughout the studies, at 32·3 ± 0·2°C for the median nerve studies and 31·2 ± 0·6°C for the sural nerve studies.
Stimulation
The computer was programmed to deliver different stimuli or stimulus combinations in rotation at 1 Hz. A fixed supramaximal stimulus of 0·2 ms duration was delivered on channel 1, and unconditioned test stimuli of 1 ms duration were delivered on channel 2, the strength of the stimulus being maintained by the computer to produce a CSAP of 50 % of maximum. On further channels, long-lasting depolarizing and/or hyperpolarizing current pulses were delivered in isolation. On still further channels test stimuli of 1 ms duration were delivered before, during and after these conditioning current pulses, and the test CSAP was measured after subtraction of the artifact produced by the depolarizing or hyperpolarizing conditioning currents delivered in isolation. The subtraction was particularly necessary for the sural studies because decay of the large stimulus artifact produced a sloping baseline distorting the test CSAP. The same procedure was therefore used for median studies. The intensity of the test stimuli was adjusted to produce a CSAP of 50 % of maximum, as on channel 2, using proportional tracking (Bostock et al. 1998).
Conditioning stimuli
The intensity of the depolarizing and hyperpolarizing DC was set as a percentage of the threshold for the unconditioned CSAP on stimulus channel 2. In different studies, the DC polarization lasted 150 ms (e.g. Fig. 2), 300 ms (e.g. Fig. 1) or 330 ms (as for Figs 3-5). The full threshold electrotonus waveforms were determined simultaneously for two or three conditioning current intensities (as in Figs 1 and 2), by measuring the changes in threshold produced by DC before, and at various intervals during and after the conditioning current.
In further studies, the threshold changes were measured at only three conditioning-test intervals, i.e. 25, 100 and 300 ms after the onset of DC polarization, using rectangular current pulses that lasted 330 ms. The intensity of the polarizing current was changed from 0 to 35 % (in the depolarizing direction) in 5 % steps and from 0 to -100 % (in the hyperpolarizing direction) in 10 % steps. As illustrated in Fig. 1, the three threshold measurements sampled the threshold electrotonus waveform where the threshold reduction to depolarizing currents was maximal (
25 ms), where the threshold increase to hyperpolarizing currents was maximal (100 ms), and at an interval at which accommodative changes in threshold due to slowly activated conductances would be clear (300 ms).
Nomenclature
The phases of threshold electrotonus and their measurements are illustrated in Fig. 1, which shows the threshold changes produced by polarizing currents lasting 300 ms, with intensities of +40 % (depolarizing) and -40 and -80 % (hyperpolarizing) of the threshold for the unconditioned CSAP. The conditioning current is illustrated in the lower panel of Fig. 1. To emphasize the analogy with the electrotonic potentials that are responsible for the changes in threshold, threshold electrotonus is plotted as 'threshold reduction', with the decrease in threshold produced by depolarizing currents upwards and the increase in threshold produced by hyperpolarizing currents downwards (see Bostock & Baker, 1988; Bostock et al. 1998). The phases of threshold electrotonus illustrated in Fig. 1 are defined as follows.
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Threshold electrotonus of median ( | ||
F: the abrupt threshold change due to the rapid depolarization or hyperpolarization of the nodes of Ranvier corresponding to the first electrotonic response to the polarizing current.
S1 (depolarizing): first slow component of threshold electrotonus produced by depolarizing current (T25d - F).
S1 (hyperpolarizing): first slow component of threshold electrotonus produced by hyperpolarizing current (T100h - F).
S2: second slow component which reflects the accommodation to depolarizing potential changes (T25d - T300d).
S3: third slow component due to inward rectification activated by hyperpolarization (T100h - T300h).
T25, T100 and T300 represent the normalized thresholds measured 25, 100 and 300 ms, respectively, after the onset of depolarizing (d) or hyperpolarizing (h) currents.
It is not implied that the conductances responsible for the accommodative processes, largely a slow K+ conductance with depolarization and inward rectification with hyperpolarization, are not active until 25 and 100 ms, respectively. However, the changes in membrane potential driving the conductances are probably greatest at these latencies, and the accommodative changes in membrane potential due to the conductances are presumably related to the differences in thresholds measured at these latencies and at 300 ms.
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RESULTS |
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Sequence and rationale for the studies
Threshold electrotonus was measured in two series of identical experiments using prolonged depolarizing currents lasting 150 ms. Accommodation to depolarizing currents (S2) and the threshold undershoot when the current ended were greater for median afferents than for sural afferents, findings that were not unexpected given previous studies on the recovery of excitability following suprathreshold stimuli (Lin et al. 2000). However, the S1 phase of threshold electrotonus was also significantly greater for median afferents. To investigate this further and to look for differences in accommodation to hyperpolarizing currents, further studies were performed using prolonged hyperpolarizing and depolarizing currents lasting 300 ms. These studies established that S1 was, indeed, greater for median afferents for both depolarizing and hyperpolarizing currents and that accommodation to the hyperpolarizing current (S3) was also greater for median afferents. This raised the possibility that the differences in accommodation to depolarizing and hyperpolarizing currents were merely because the applied currents produced greater changes in membrane potential for median afferents. To address this possibility, the changes in threshold were measured at specific intervals in response to DC polarization of 330 ms duration and of graded intensity, from 0 to 35 % in 5 % steps in the depolarizing direction and from 0 to -100 % in 10 % steps in the hyperpolarizing direction.
Threshold changes produced by prolonged subthreshold depolarizing currents
To look for evidence for a difference in accommodation to prolonged depolarizing currents, the changes in threshold produced by subthreshold DC lasting 150 ms were measured in eight subjects using conditioning currents that were 20 and 40 % of threshold (Fig. 2A). The fast phase of threshold electrotonus (F) was the same for the two nerves, directly proportional to the applied current, but the subsequent slow phase (S1) was greater for median afferents. During S1 there was a further depolarizing threshold change (see Bostock & Baker, 1988; Baker & Bostock, 1989; Bostock et al. 1998), and the maximal threshold reduction produced by the DC was greater for median afferents for both depolarizing currents. The peak of S1 occurred earlier the greater the size of S1, irrespective of whether the responses to polarizing currents of different intensity (40 vs. 20 %) or the responses of the two nerves (median vs. sural) were compared.
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A, mean data (±S.E.M.) for eight subjects; | ||
The subsequent decay in the threshold reduction (S2) represents accommodation to the depolarizing change in membrane potential and was greater for median afferents. The threshold changes at the end of the DC pulses can be considered equivalent to 'tail currents' (though presumably they cannot be attributed with certainty to a single conductance). The threshold undershoot on cessation of the 150 ms subthreshold conditioning current was greater for median than for sural afferents, as would be expected if slow conductances de-activated gradually following the end of the polarizing current. Importantly, however, the threshold plateau level at the end of the depolarizing current was similar for the two nerves, suggesting that the differences in the size of the undershoots cannot be attributed to starting from different membrane potentials.
The data in Fig. 2A are quantified in Fig. 2C-E. The peak threshold reduction, S2 accommodation and threshold undershoot were each significantly greater for the median nerve (P = 0·0013, P = 0·0014, P = 0·0038, respectively; ANOVA: two factor with replication). The differences in S2 (Fig. 2D) and in the threshold overshoot (Fig. 2E) are those expected if the conductance responsible for the accommodation was more active on median afferents. To confirm the unexpected difference in S1, the same experiment was repeated on six subjects (2 'naïve' subjects and 4 who had participated in the experiments shown in Fig. 2A). The results were virtually identical (Fig. 2B).
Responses to subthreshold depolarizing and hyperpolarizing currents lasting 300 ms
The differences in S1d and S1h shown in Fig. 1 suggest that the applied currents produce greater changes in membrane potential in the median nerve than in the sural nerve. If this is the case, the differences in accommodation seen in the figure (in both S2 and S3) might be expected if the accommodative changes depended on voltage-dependent conductances (slow K+ conductance and inward rectification with depolarizing and hyperpolarizing changes in membrane potential, respectively).
Responses to graded depolarizing and hyperpolarizing currents
In eight subjects, depolarizing and hyperpolarizing currents of 330 ms duration were varied in intensity, from 0 to 35 % in 5 % steps in the depolarizing direction and from 0 to -100 % in 10 % steps in the hyperpolarizing direction. The threshold changes were measured 25 ms after the onset of the subthreshold current (representing the peak of the S1 phase in the depolarizing direction, i.e. S1d), 100 ms after the start of the subthreshold current (representing the peak of S1 in the hyperpolarizing direction, i.e. S1h) and at 300 ms. The slow K+ conductance believed to be responsible for accommodation to depolarizing threshold changes (S2) is located on both the node and the internode (Baker et al. 1987; Röper & Schwarz, 1989; see Bostock, 1995; Bostock et al. 1998), and the change in membrane potential 'driving' S2 is presumably reflected in the total threshold change, i.e. F + S1d. However, inward rectification is primarily an internodal conductance (Baker et al. 1987; Bostock, 1995; Pape, 1996), and S1h (rather than F + S1h) is probably a more appropriate reflection of the change in membrane potential 'driving' S3. (Nevertheless, the differences between the responses of the two nerves described below were similar whether S1h or F + S1h was used to indicate the change in membrane potential responsible for the accommodation.)
In Figs 3A and 4A, the data using graded changes in polarizing current confirm that the changes in threshold produced by depolarizing and hyperpolarizing currents were greater for median afferents. The 35 % depolarizing current produced a maximal threshold reduction of 64 ± 2 % for median afferents but only 50 ± 3 % for sural afferents (P = 0·0088, Student's paired t test). The 100 % hyperpolarizing current increased the threshold of median afferents by 331 ± 14 % and that of sural afferents by 292 ± 13 % (P = 0·0121). Note that, in Fig. 4A, the increase in threshold is plotted as the change in 'S1h' rather than the total threshold increase, as discussed above.
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In A, F + S1d is the threshold measured 25 ms after the onset of depolarizing current. In B, S2 is the difference between thresholds measured 25 and 300 ms after the onset of the depolarizing current. Data are for the median nerve ( | ||
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In A, S1h is the threshold measured 100 ms after the onset of hyperpolarizing current minus the fast (F) threshold change. In B, S3 is the difference between thresholds measured 100 and 300 ms after the onset of the hyperpolarizing current. Data represent means ± S.E.M. for the median nerve ( | ||
The data in Figs 3B and 4B demonstrate that median afferents undergo greater accommodation than sural afferents with both depolarizing and hyperpolarizing currents. Accommodation to the 35 % depolarizing current brought the median threshold down from 64 ± 2 % at 25 ms to 43 ± 2 % at 300 ms, a greater change than occurred with sural afferents (50 ± 3 % at 25 ms and 37 ± 2 % at 300 ms; P = 0·0307, Student's paired t test). Similarly, accommodation to the strongest hyperpolarizing current resulted in threshold increases of 252 ± 9 % at 300 ms (down from 331 ± 14 % at 100 ms) for median afferents, and of 240 ± 12 % at 300 ms (down from 292 ± 13 %) for sural afferents (P = 0·0019).
In Fig. 5, the extent of accommodation is plotted against the change in threshold that was presumably 'driving' the accommodation, on the assumption that the change in threshold reflected the underlying change in membrane potential. With both depolarization (Fig. 5A) and hyperpolarization (Fig. 5B), the relationships were approximately linear, with r2 values > 0·98. As a result of the greater threshold change produced in median afferents by the DC polarization, the median data extend along the X-axis beyond the sural data. The difference between the slopes of the relationships was significant (P (same slope) = 0·0134 and < 0·001, respectively; Student's t test on confidence interval for the difference between the slopes of the regression lines; Gardner & Altman, 1989), suggesting that, for the same threshold change, median afferents would undergo 22·4 % more accommodation to depolarizing currents and 28·7 % more accommodation to hyperpolarizing currents than sural afferents.
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A, responses to depolarizing currents. F + S1d is the threshold measured 25 ms after the onset of the depolarizing current, presumably reflecting the change in membrane potential that drives S2. The relationship between the S2 accommodation and F + S1d is approximately linear for both nerves. The probability that the two lines have the same slope is 0·0134. B, responses to hyperpolarizing currents. S1h is the threshold change measured 100 ms after the onset of the hyperpolarizing current minus F, the fast phase, and presumably reflects the change in membrane potential that drives S3. The relationship between the S3 accommodation and S1h is approximately linear for both nerves. The probability that they have the same slope is < 0·001. | ||
We therefore conclude that median afferents accommodate more to depolarizing and hyperpolarizing currents than sural afferents, even when the different changes in membrane potential produced by those currents are factored out.
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DISCUSSION |
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The present study has demonstrated significant biophysical differences between large myelinated cutaneous afferents in the median and sural nerves using threshold electrotonus, the only physiological technique that allows one to explore internodal properties in human subjects. Firstly, currents of equivalent intensity produce different changes in threshold and presumably therefore different changes in membrane potential. Secondly, accommodation to these currents is greater on median afferents than on sural afferents, and remains so when any difference in membrane potential is controlled. It will be argued below that the difference in accommodation to depolarizing currents results from a difference in a slow K+ conductance, and the difference in accommodation to hyperpolarizing currents results from a difference in inward rectification, and that these biophysical differences could result in differences in susceptibility to disease or injury.
An assumption of the present study was that the changes in threshold produced by long-lasting DC polarization parallel the underlying changes in membrane potential. This assumption seems well based, though it may not be so when axons are significantly depolarized (Baker & Bostock, 1989).
Why do polarizing currents produce different changes in membrane potential in median and sural afferents?
Polarizing currents produced greater changes in the threshold of median afferents than in that of sural afferents, and the extent of accommodation was greater on median afferents with both depolarizing and hyperpolarizing currents. As discussed below, the differences in S1 are probably not the result of a difference in resting membrane potential. However, given the differences in S1, differences in accommodation might be expected because the accommodative responses are due to the activation of voltage-dependent conductances, and presumably the conductances on median afferents would have been subjected to greater changes in membrane potential. However, an important finding of the present study is that the difference in S1 is not a sufficient explanation for the differences in accommodation.
The fast (F) phase of threshold electrotonus was identical for the two nerves suggesting that there was little difference in the access to the nodal membrane for the two nerves. S1 results from the slow depolarization of the internodal membrane and the effects of this on nodal excitability. Many factors could contribute to the differences in S1: morphological factors altering access to the internodal membrane (e.g. myelination), differences in the properties of the internodal membrane (e.g. axonal size and internodal length, the resistance of the internodal axolemma, differences in resting membrane potential) and unsuspected technical factors.
The fastest afferents in the sural nerve have a slower conduction velocity than those in the median nerve (50 and 59 m s-1 for the CSAPs in the present study), and presumably a slightly smaller average diameter. At the stimulation sites, large median axons generally have diameters of < 20 µm (Buchthal & Rosenfalck, 1966) and sural axons diameters of < 16 µm (O'Sullivan & Swallow, 1968). However, the smaller axonal size would be expected to increase internodal resistance and thereby increase S1 (Barrett & Barrett, 1982; Yang et al. 2000), the opposite of the present finding. In addition, in a parallel study (Lin et al. 2000), it has been found that there are no differences between median and sural afferents in refractoriness, an excitability parameter that depends on size (Paintal, 1965, 1966; Brink & Mackel, 1993; see also Buchthal & Rosenfalck, 1966).
Temperature is unlikely to be a factor because the skin temperature did not differ significantly for the studies in this series. Temperature can have prominent effects on some measures of axonal excitability (such as refractoriness), but not all (Burke et al. 1999). It is relevant that threshold electrotonus is not sensitive to differences in temperature within the range 30-34°C (Kiernan et al. 2000).
A difference in resting membrane potential would alter threshold electrotonus. If sural afferents were more depolarized, S1 would be less because depolarization would activate voltage-dependent K+ channels on the internodal membrane, thereby decreasing its resistance (Baker & Bostock, 1989; Horn et al. 1996; Bostock et al. 1998). However, in a parallel study, the extent of refractoriness and supernormality were found to be the same on median and sural afferents (Lin et al. 2000). Both are sensitive to changes in membrane potential (and refractoriness is particularly so; Burke et al. 1998). In addition, a difference in the fast phase of electrotonus might have been expected (Baker et al. 1987) but, as noted above, there was no difference in the fast phase (F) of threshold electrotonus. Finally, if resting membrane potential differed, accommodation to depolarizing and hyperpolarizing currents would not both be greater on median afferents.
The difference in S1 could imply that current does not access internodal structures equally and, if so, it is possible that this biophysical difference has a morphological explanation. Alternatively, blocking paranodal fast K+ channels will increase the resistance of the internodal membrane and increase S1 (Baker et al. 1987; Bostock, 1995; Horn et al. 1996). However, if there were fewer functioning paranodal K+ channels on median axons, supernormality would also be enhanced (Barrett & Barrett, 1982; David et al. 1995), and the available evidence is against this (Lin et al. 2000). The precise mechanism by which S1 differs for the two nerves, and whether it lies primarily in axonal properties or in myelination, remains conjectural. Regardless of mechanism, the difference in S1 implies that the change in membrane potential driving accommodation differs for the two nerves.
Accommodation to depolarizing currents
The S2 phase of accommodation to long-lasting subthreshold depolarizing currents is largely due to the activation of a slow K+ conductance (Bostock, 1995), as is the threshold undershoot on termination of the current (the threshold analogue of a tail current). Slow K+ channels are found on both nodal and internodal membranes (see Röper & Schwarz, 1989; Safronov et al. 1993; Vogel & Schwarz, 1995; Reid et al. 1999). Their activation produces an outward K+ current that shifts the membrane potential back towards the resting level when axons are subjected to prolonged depolarization (i.e. they have a 'hyperpolarizing' action).
Based on studies using single suprathreshold conditioning stimuli and trains of such stimuli, Lin et al. (2000) presented evidence that the nodal slow K+ conductance is greater on median afferents than on sural afferents. The present results are in accord with these previous findings but could not have been predicted with confidence given the greater number of slow K+ channels on the internode. The present findings indicate that the expression of the slow K+ conductance may be low on both the internodal and nodal membranes.
Accommodation to hyperpolarizing currents
The S3 phase of accommodation to long-lasting subthreshold hyperpolarizing currents is largely due to inward rectification (Bostock, 1995). Inward rectification behaves in an anomalous voltage-dependent manner: it is activated slowly by hyperpolarization, the more so the greater the hyperpolarization, and it operates as a depolarizing conductance, restoring the membrane potential back towards the resting level (Pape, 1996). In axons, the conductance is located in the internodal region (Baker et al. 1987; Birch et al. 1991) and is permeable to both Na+ and K+ ions, and its biological role is probably to limit the extent of hyperpolarization that occurs when axons conduct trains of impulses (Pape, 1996; see Kiernan et al. 1997; Vagg et al. 1998).
A difference in inward rectification could not have been anticipated from previous studies because behaviour due to internodal conductances can only be investigated in vivo in human subjects with threshold electrotonus (Bostock, 1995; Bostock et al. 1998). Nevertheless, S3 was significantly greater for median afferents even when the driving threshold change (S1h) was matched (this was also the case when S3 was plotted against F + S1h). It is therefore likely that two internodally located conductances, one responsible for accommodation to depolarizing currents and one responsible for accommodation to hyperpolarizing currents are expressed more on cutaneous afferents in the median nerve than on those in the sural nerve.
Functional implications and clinical relevance
The present study provides evidence that cutaneous afferents in the median and sural nerves react differently to long-lasting depolarizing and hyperpolarizing stimuli, and that two accommodating conductances are more active on the median nerve. Depolarization and hyperpolarization produced greater changes in membrane potential for the median nerve, and potentially median afferents would be more unstable than sural afferents without the accommodation. However, accommodation was greater on median than sural afferents for similar changes in threshold (and presumably for similar changes in membrane potential). As a result it is likely that the greater expression of these conductances on median afferents confers greater stability.
Cutaneous afferents in the median and sural nerves serve different sensory and motor roles. Median afferents are critically involved not only in cutaneous sensibility but also in manual dexterity (see, e.g. Johansson et al. 1994; Macefield et al. 1996; McNulty et al. 1999). The skin innervated by the sural nerve is commonly protected by socks and shoes and is probably subjected to a totally different pattern of mechanical stimulation. Presumably, cutaneous afferents in the two nerves normally maintain quite different patterns of impulse activity, and it is possible that the differences explored in the present paper represent adaptations to these different patterns of usage.
The clinical manifestations of acquired polyneuropathies are generally more severe distally in the lower limb. With axonopathies and neuronopathies, this distribution is attributed to the greater length of the axon and the greater metabolic load that is therefore placed on the dorsal root ganglion cell (Thomas & Ochoa, 1993). With demyelinating polyneuropathies, it is possible to explain this distal distribution if segments of demyelination occur randomly in axons, because this would place longer axons with more myelin segments in greater jeopardy (Waxman et al. 1976). The present study points to biophysical differences between cutaneous afferents innervating the distal upper and lower limbs, and it is conceivable that these differences confer a difference in the ability of the afferents to handle stress. It is likely that factors other than axonal length contribute to the distal lower limb distribution of symptoms and signs in acquired polyneuropathies.
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REFERENCES |
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This study was supported by the National Health and Medical Research Council of Australia, the National Multiple Sclerosis Association of Australia and the Uehara Memorial Foundation of Japan.
Corresponding author
D. Burke: Prince of Wales Medical Research Institute, High Street, Randwick, Sydney, NSW 2031, Australia.
Email: d.burke{at}unsw.edu.au
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) and sural (
) cutaneous afferents from a single subject. The threshold required to produce a compound sensory action potential of 50 % of maximum was measured using test stimuli of 1·0 ms duration. The changes in threshold were produced by polarizing currents of 300 ms duration with intensities of +40, -40 and -80 % of the unconditioned threshold, as shown in the bottom panel. The symbols F, S1d, S1h, S2 and S3 are defined as shown for the responses of median afferents to 40 % depolarizing and 80 % hyperpolarizing currents (see also text). The three vertical lines were drawn at 25, 100 and 300 ms, i.e. at the peak of S1d, at the peak of S1h and at the end of the polarizing currents, respectively. d and h denote the depolarizing and hyperpolarizing direction, respectively.
, median; 
, sural). 'Peak' refers to the maximal threshold decrease and corresponds to the peak of S1d. S2 represents the difference between the peak threshold and the threshold at 150 ms. The 'off response' was measured 25-30 ms after the end of the DC pulse.