RESUMEN
The objective was to determine biophysical differences between fast and slow motor axons using threshold tracking and demonstrate confounds related to anesthetic. Nerve excitability of motor axons innervating the slow-twitch soleus (SOL) and fast-twitch tibialis anterior (TA) muscles was tested. The experiments were conducted with pentobarbital sodium (SP) anesthetic and compared with previous results that used ketamine-xylazine (KX). Nerve excitability indices measured with SP show definitive differences between TA and SOL motor axons that extend beyond previous reports. Nerve excitability indices sensitive to changes in Ih indicated an increase in SOL axons compared with TA axons [e.g., S3 t = 7.949 (df = 10), P < 0.001; hyperpolarizing threshold electrotonus (90-100 ms), t = 2.659 (df = 20); P = 0.01; hyperpolarizing I/V slope, t = 4.308 (df = 19); P < 0.001]. SOL axons also had a longer strength-duration time constant [t = 3.35 (df = 20); P = 0.003] and a longer and larger magnitude relative refractory period [RRP (ms) t = 3.53 (df = 12); P = 0.004; Refractoriness at 2 ms, t = 0.0055 (df = 9); P = 0.006]. Anesthetic choice affected many measures of peripheral nerve excitability with differences most apparent in tests of threshold electrotonus and recovery cycle. For example, recovery cycle with KX lacked a clear superexcitable and late subexcitable period. We conclude that KX had a confounding effect on nerve excitability results consistent with ischemic depolarization. Results using SP revealed the full extent of differences in nerve excitability measures between putative slow and fast motor axons of the rat. These results provide empirical evidence, beyond conduction velocity, that the biophysical properties of motor axons vary with the type of muscle fiber innervated. These differences suggest that fast axons may be predisposed to dysfunction during hyperpolarizing stresses, e.g., electrogenic sodium pumping following sustained impulse conduction.NEW & NOTEWORTHY Nerve excitability testing is a tool used to provide insight into the properties of ion channels in peripheral nerves. It is used clinically to assess pathophysiology of axons. Researchers customarily think of motor axons as homogeneous; however, we demonstrate there are clear differences between fast and slow axons in the rat. This is important for interpreting results with selective motor neuronopathy, like aging where fast axons are at high risk of degeneration.
Asunto(s)
Potenciales de Acción , Axones/fisiología , Neuronas Motoras/fisiología , Animales , Axones/clasificación , Axones/efectos de los fármacos , Femenino , Ketamina/farmacología , Neuronas Motoras/efectos de los fármacos , Fibras Musculares de Contracción Rápida/fisiología , Fibras Musculares de Contracción Lenta/fisiología , Nervios Periféricos/efectos de los fármacos , Nervios Periféricos/fisiología , Ratas , Ratas Sprague-Dawley , Canales de Sodio/metabolismo , Xilazina/farmacologíaRESUMEN
Much is known about the electrophysiological variation in motoneuron somata across different motor units. However, comparatively less is known about electrophysiological variation in motor axons and how this could impact function or electrodiagnosis in healthy or diseased states. We performed nerve excitability testing on two groups of motor axons in Sprague-Dawley rats that are known to differ significantly in their chronic daily activity patterns and in the relative proportion of motor unit types: one group innervating the soleus ("slow motor axons") and the other group innervating the tibialis anterior ("fast motor axons") muscles. We found that slow motor axons have significantly larger accommodation compared to fast motor axons upon application of a 100 ms hyperpolarizing conditioning stimulus that is 40% of axon threshold (Z = 3.24, p = 0.001) or 20% of axon threshold (Z = 2.67, p = 0.008). Slow motor axons had larger accommodation to hyperpolarizing currents in the current-threshold measurement (-80% Z = 3.07, p = 0.002; -90% Z = 2.98, p = 0.003). In addition, we found that slow motor axons have a significantly smaller rheobase than fast motor axons (Z = -1.99, p = 0.047) accompanied by a lower threshold in stimulus-response curves. The results provide evidence that slow motor axons have greater activity of the hyperpolarization-activated inwardly rectifying cation conductance (IH) than fast motor axons. It is possible that this difference between fast and slow axons is caused by an adaptation to their chronic differences in daily activity patterns, and that this adaptation might have a functional effect on the motor unit. Moreover, these findings indicate that slow and fast motor axons may react differently to pathological conditions.