3. Characterization of persistent Na+ current in human motor and sensory axons: Exploring the activity at different target levels

Abstract

Introduction Axonal excitability studies are useful clinical tool for the understanding of the physiology of myelinated axons. Across all nerve excitability parameters, the strength-duration time constant (SDTC) has been shown to be related to the activity of persistent Na + (Na p ) current. Na p currents have been implicated in several diseases including ALS, SMA and Kennedy’s disease. Because SDTC can also be affected by passive membrane properties, latent addition (LA) is considered a better method, as it is able to separately evaluate Na p and passive membrane properties. Many studies examine the properties of axons recruited at 40% of maximal amplitude, however information about the expression of Na p in different population of axons is still missing. Objective To characterize Na p currents in motor and sensory axons at different target levels. Methods Motor and sensory nerve excitability studies were recorded using threshold tracking techniques in 22 healthy controls (mean age 32.3 ± 7.5 years (mean ± S.D.), 11 males). The median nerve was stimulated at the wrist, with CMAPs and CSAPs recorded distally. An axonal excitability protocol was conducted, which included assessment of strength-duration properties and latent addition. These properties were studied in different populations of axons at 10%, 20%, 40%, and 60% of the maximal response for both motor and sensory nerve. Results Maximal amplitudes were 8.8 ± 0.7 mV and 81.8 ± 6.6 μ V (mean ± SEM) for CMAP and CSAP, respectively. Motor SDTCs were longer at lower target levels (10%: 0.42 ms, 20%: 0.41 ms, 40%: 0.40 ms, 60%: 0.37 ms, F = 9.0, p = 0.002). This relationship was more prominent in sensory axons (10%: 0.69 ms, 20%: 0.65 ms, 40%: 0.58 ms, 60%: 0.54 ms, F = 67.4, p 0.0001). The passive membrane properties were similar for both motor and sensory between different target levels. Threshold changes at 0.2 ms, the best measure of Nap conductance, were higher in sensory axons than in motor (motor vs sensory: 10%: 10.8 vs 17.6, 20%: 10.6 vs 17.2, 40%: 11.9 vs 17.3, 60%: 12.2 vs 17.6), but there was no correlation between Nap and target level in either motor or sensory nerve (motor, F = 1.85, p = 0.18; sensory, F = 0.25, p = 0.78). Regression analyses showed significant relationships between threshold change at0.2 ms and SDTC at all target level for both motor and sensory (R 2 (motor) 10%: 0.68, 20%: 0.47, 40%: 0.50, 60%: 0.65, R 2 (sensory) 10%: 0.76, 20%: 0.71, 40%: 0.80, 60%: 0.70). Conclusions This study provides a comprehensive assessment of Na p current in motor and sensory axons of differing target levels. SDTC was inversely correlated with target level, however threshold change at 0.2 ms was not, suggesting that differences in SDTC between different populations of axons are not fully explained by changes in Na p current.