Journal List > Ann Clin Neurophysiol > v.19(1) > 1099490

Burke, Howells, and Kiernan: Sensory and motor axons are different: implications for neurological disease

초록

Using threshold tracking, differences have been established between large myelinated sensory and α motor axons in humans. Major differences are that sensory axons are relatively de-polarised at rest such that they have a greater persistent Na+ current, and have greater activity of hyperpolarisation-activated cyclic nucleotide-gated (HCN) channels. Sensory axons may thereby be protected from hyperpolarising stresses, and are less likely to develop conduction block. However, the corollary is that sensory axons are more excitable and more likely to be-come ectopically active.

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Fig. 1.
Distribution of voltage-dependent ion channels.
acn-19-3f1.tif
Fig. 2.
Excitability measures for sensory and motor axons. (A) Extended excitability data for motor (●) and sensory (○) axons (n = 10; mean ± SEM [dashed lines]), both recorded using 1 ms test stimuli. (A) threshold electrotonus for conditioning levels of ± 40%, −70% and −100% of control threshold. (B) current–threshold (I–V) relationship for 100 ms and 200 ms conditioning stimuli. The 100 ms conditioning stimuli resulted in a larger decrease in excitability at −100% as less accommodation to hyperpolarization developed over the shorter time span. Note the greater accommodation of sensory axons in A and B. (C) Strength–duration time constant for motor (filled symbols) and sensory (open symbols) studies. Means (continuous lines) ± SEM (dotted lines). Data from published normal control studies are presented on the left (squares). Data from the 10 subjects in the present study (circles; lines link the same subject). The data on the right are the strength–duration time constants as estimated by the mathematical model for sensory and motor axons (triangles). Modified from reference15 with permission. SEM, standard error of the mean.
acn-19-3f2.tif
Fig. 3.
Individual motor nerve recordings and motor model. Individual motor nerve recordings (n = 10) of extended threshold electrotonus (A) (conditioning levels of ± 20%, ± 40%, −70% and −100% of unconditioned threshold), and I–V (C) (for clarity, only the 200 ms conditioning stimulus data is dis-played). Threshold electrotonus (B) and I–V (D) as generated by the motor axon model with variation of the voltage for half-activation of I h from −87.3 to −127.3 mV in 5 mV steps. Reused from reference15 with permission.
acn-19-3f3.tif
Fig. 4.
Activity-dependent hyperpolarisation of motor axons due to voluntary contraction. The median nerve was stimulated at the wrist and a 70% CMAP was tracked over the thenar muscles, using increments and decrements in stimulus intensity of 2%. In each panel, maximal voluntary contractions were performed 5 min after the onset of the traces. The increase in the normalised threshold represents the increase in current required to produce the control CMAP, and this reflects the axonal hyperpolarisation. The extent of hyperpolarisation and its duration depend on the duration of contraction (i.e., the impulse load). In A, B and C, the contractions lasted 15, 30 and 60 s, respectively. Each trace represents mean data for six subjects. Reused from reference23 with permission. CMAP, compound muscle action potential; MVC, maximal voluntary contraction.
acn-19-3f4.tif
Fig. 5.
Activity-dependent changes in threshold for motor and sensory axons. Mean changes in threshold (± SEM) recorded for 9 subjects following repetitive stimulation of the median nerve at the wrist at 8 Hz for 10 min. Changes are shown for motor (A) and sensory axons (B) using test stimuli of 0.1 and 1 ms duration. Immediately following cessation of impulse trains, axons became less excitable, with a prominent increase in threshold, significantly greater for motor axons when compared to sensory. Reused from reference24 with permission. SEM, standard error of the mean.
acn-19-3f5.tif
Fig. 6.
The development of conduction block in a human muscle spindle afferent. Raster display of action potentials of a muscle spindle afferent from extensor pollicis longus developing and recovering from conduction block. The muscle spindle afferent discharged irregularly at ~3 Hz when mild pressure was applied to the receptor. The action potential had two peaks generated at nodes of Ranvier on either side of the site of impaled internode.28 The separation of the peaks therefore reflects internodal conduction time, and its pro-longation indicates the security of transmission. When conduction across the impaled internode was blocked the recorded potential consists of only a single peak generated proximal to the site of im-palement. When the pressure was increased (Pressure on), 10 min after the onset of the recording, the discharge rate of the afferent increased to ~20 Hz, and the second positive peak became unstable and disappeared. When pressure was relaxed (Pressure off), the second peak reappeared, only to disappear 2 min later when pressure was again increased. The longest interpeak interval was 975 μs in the first episode and 1.02 ms immediately after the second episode. The illustrated sequence contains 891 consecutive action potentials. Modified from reference27 with permission.
acn-19-3f6.tif
Table 1.
How does activity affect axons?
acn-19-3f7.tif
Table 2.
Physiological manoeuvres that can precipitate or worsen conduction block
Conduction block during axonal hyperpolarization
Activity-dependent hyperpolarization
Can increase threshold by ~40%
Can accentuate conduction block in MMN and CIDP
Can account for fatigue and fading of strength
Post-ischaemic hyperpolarization
Can increase threshold by ~20-30%
Can accentuate conduction block in CIDP
Relationship between the degree of block and the increase in threshold is the same as for activity
Conduction block due to changes in the Na+ current
Reduced availability of functioning Na+ channels
Blockade of Na+ channels – e.g., local anaesthetics, ischaemic metabolites, puffer fish poisoning (TTX)
Conduction block during ischaemic depolarization – due toinactivation of Na+ channels and possibly theirblockade by ischaemic metabolites
Conduction block due to changes in the time course of the Na+ current
Temperature-induced changes in the Na+ current: decreased time integral of the Na+ current with fever
MMN, multifocal motor neuropathy; CIDP, chronic inflammatory demyelinating polyneuropathy.
Table 3.
Testing for conduction block
Ensure that the limb is warm
Test for fixed conduction block with supramaximal stimuli
Test for variable conduction block with supramaximal stimuli
If only one stimulus, its strength should be > 40% supramaximal
If two, the second stimulus should 20% higher than the first
Deliver the stimuli at 1/s (alternating if there are two stimuli), before and after maximal voluntary contraction of the test muscle for 1 min
On a separate day, deliver stimuli at 1/s before, during and after ischaemia of the limb for 10 min
? Repeat studies after warming
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