Nerve Excitability Differences in Slow and Fast Motor Axons of the Rat: more than just Ih

Abstract

ObjectiveThe objective was to determine if choice of anaesthetic confounded previous conclusions about the differences in nerve excitability indices between fast and slow motor axons.\n\nMethodologyNerve excitability of the rat sciatic nerve was tested while measuring responses of motor axons innervating the slow-twitch soleus (SOL) and fast-twitch tibialis anterior (TA) muscles. The experiments were conducted with sodium pentobarbital (SP) anaesthetic and compared to previous results that used ketamine-xylazine (KX).\n\nResults and ConclusionsPrevious conclusions about the differences in nerve excitability indices between TA and SOL motor axons using KX were corroborated and extended when experiments were done with SP. Nerve excitability indices sensitive to changes in hyperpolarization-activated inwardly rectifying cation current (Ih) indicated an increase in Ih in SOL axons compared to TA axons (e.g. S3 (-100 %), t=7.949 (df=10), p < 0.0001; TEh (90-100 ms), t=2.659 (df=20), p = 0.0145; hyperpolarizing I/V slope, t=4.308 (df=19), p = 0.0004). SOL axons also had a longer strength-duration time constant (t=3.35 (df=20), p = 0.0032) and a longer and larger magnitude relative refractory period (RRP (ms) t=3.53 (df=12), p = 0.0041; Refractoriness at 2 ms t=0.0055 (df=9), p = 0.0055).\n\nAnaesthetic 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 ischaemic 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 differences have important implications for the use of nerve excitability measures during processes such as ageing where it is believed that there is a selective loss of fast axons.\n\nNew & NoteworthyNerve 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 motor 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.