Latent addition in human motor and sensory axons: Different site-dependent changes across the carpal tunnel related to persistent Na+ currents

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Abstract

Objective

To compare site-dependent changes across the carpal tunnel in axonal persistent Na+ conductances in motor and sensory axons. Positive sensory symptoms are prominent features in carpal tunnel syndrome, and a persistent Na+ current is a major determinant of axonal excitability.

Methods

The technique of latent addition was used to estimate persistent Na+ currents in median motor and sensory axons at the wrist and palm of 10 normal subjects. Brief hyperpolarizing conditioning current pulses were delivered, and threshold change at the conditioning-test interval of 0.2 ms was measured as an indicator of persistent Na+ currents.

Results

Threshold changes at 0.2 ms were greater in sensory than in motor axons at both the wrist and palm. In motor axons, the threshold changes were significantly smaller at the palm (mean, 4.9%) than at the wrist (10.0%). By contrast, the threshold changes were similar at the two sites of sensory axons (12.6 and 13.1%). The passive membrane time constant was similar for motor and sensory axons at the palm and wrist.

Conclusions

Nodal persistent Na+ conductances have substantial site-dependent changes decreasing distally across the carpal tunnel in median motor axons, but not in sensory axons.

Significance

Whereas sensory axons generally have higher excitability than motor axons, the sensory-motor differences become more prominent across, and possibly at the carpal tunnel than the nerve trunk, and it is suggested that this contributes to the predominance of positive sensory symptoms in carpal tunnel syndrome.

Introduction

There is evidence that axonal excitability properties are different in human motor and sensory axons (Mogyoros et al., 1997). Sensory axons have less supernormality and late subnormality following a single conditioning stimulus (Kiernan et al., 1996), longer strength–duration time constant (mean, 665 versus 459 μs for motor axons; Mogyoros et al., 1996), greater inward rectification (Bostock et al., 1994), and greater expression of persistent Na+ channels (Bostock and Rothwell, 1997). Because of these differences, their responses to injury or compression would differ. Especially due to greater persistent Na+ channels and inward rectification, sensory axons more easily generate ectopic activity. In peripheral neuropathies, positive sensory symptoms such as paresthesia and pain are usually more prominent than positive motor symptoms such as muscle cramp, fasciculation, and myokymia. Positive sensory symptoms are prominent features particularly in carpal tunnel syndrome.

Whereas these differences have been demonstrated at the wrist portion of the median or ulnar nerve, excitability properties of axons can change along the course of the nerve (Krishnan et al., 2004, Kuwabara et al., 2000, Walters et al., 2001). Two functionally distinct types of Na+ channels are present at the nodes of Ranvier; in addition to the classical transient Na+ channels, 1.0–2.5% of the total Na+ channels, termed ‘persistent’ Na+ channels, are active at the resting membrane potential (Baker and Bostock, 1997, Crill, 1996). Previous studies showed that in median motor axons, strength–duration time constant is shorter at the palm than at the wrist, suggesting reduced persistent Na+ conductances distally (Kuwabara et al., 2004, Walters et al., 2001), but the comparison between the palm and wrist has never been made for sensory axons. The strength–duration time constant (SDTC) is a classical measure of axonal excitability and partly depends on persistent Na+ channels (Bostock et al., 1998, Kiernan et al., 2002, Mogyoros et al., 1996). However, SDTC is also affected by passive membrane properties at the nodes of Ranvier (Bostock et al., 1998, Burke et al., 2001), and therefore it has not yet been determined whether the shorter SDTC in distal motor axons results from reduced persistent Na+ currents or altered passive membrane properties.

Latent addition using automatic threshold tracking is a new technique and is currently considered the best way to non-invasively estimate nodal persistent Na+ conductance (Bostock and Rothwell, 1997, Bostock et al., 1998). We have used this technique to investigate site-dependent changes across the carpal tunnel in persistent Na+ conductances in human motor and sensory axons, and to determine whether the findings may help to account for predominance of positive sensory symptoms in carpal tunnel syndrome.

Section snippets

Subjects

Experiments were conducted on 10 normal subjects (aged 20–43 years, 4 men and 6 women) with no clinical or neurophysiological evidence of neurological disorders. All subjects gave informed consent to the experimental procedures, which had the approval of the Ethics Committee of Chiba University School of Medicine.

Latent addition

The technique of latent addition was performed using a computer program (QTRAC with multiple excitability protocol, LA99SD; copyright, Prof Hugh Bostock, Institute of Neurology,

Results

Fig. 1 shows results of latent addition (threshold change at the 0.2 ms-interval and the time constant of fast and slow components) in motor and sensory axons measured at the wrist and palm in 10 normal subjects. The time constant of the fast component was similar for motor and sensory axons at both the wrist and palm, suggesting that passive membrane properties (e.g. area of the Ranvier nodes and axonal size) do not differ significantly for motor and sensory axons and for wrist and palm axons.

Discussion

Our results showed that the in human median motor axons, threshold changes at the 0.2 ms interval in latent addition and SDTC decrease across the carpal tunnel, but did not change significantly in sensory axons. Assuming that the threshold changes at 0.2 ms in latent addition are largely determined by persistent Na+ conductances without the influences of passive membrane properties, these findings suggest that nodal persistent Na+ currents in motor axons decrease distally across the carpal

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