Properties of low‐threshold motor axons in the human median nerve

Abstract

This study investigated the excitability and accommodative properties of low-threshold human motor axons to test whether these motor axons have greater expression of the persistent Na + conductance, I NaP . Computer-controlled threshold tracking was used to study 22 single motor units and the data were compared with compound motor potentials of various amplitudes recorded in the same experimental session. Detailed comparisons were made between the single units and compound potentials that were 40% or 5% of maximal amplitude, the former because this is the compound potential size used in most threshold tracking studies of axonal excitability, the latter because this is the compound potential most likely to be composed entirely of motor axons with low thresholds to electrical recruitment. Measurements were made of the strength-duration relationship, threshold electrotonus, current-voltage relationship, recovery cycle and latent addition. The findings did not support a difference in I NaP . Instead they pointed to greater activity of the hyperpolarization-activated inwardly rectifying current (I h ) as the basis for low threshold to electrical recruitment in human motor axons. Computer modelling confirmed this finding, with a doubling of the hyperpolarization-activated conductance proving the best single parameter adjustment to fit the experimental data. We suggest that the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel(s) expressed on human motor axons may be active at rest and contribute to resting membrane potential.

In vivo evidence for reduced ion channel expression in motor axons of patients with amyotrophic lateral sclerosis

“… a ; Trevillion et al . ). These changes can, however, be explained by a failure of supply to the peripheral axon of channel and other membrane proteins from a diseased motor neuron.…”

“…Data for 31 single motor units from 21 patients with ALS (17 male, 4 female) were compared with our data for 21 single motor units from 13 healthy age‐matched controls (see Results), 17 from Trevillion et al . (). Ethical approval was obtained by the Human Research Ethics committee of the University of Sydney (no.…”

“…Isolation of single motor units is difficult in healthy subjects using Ag–AgCl surface electrodes, and the 17 units from Trevillion et al . () were recorded using a double differential recording electrode with an active sensor (DE3.1, Delsys Inc., Natick, MA, USA). The additional four control units were isolated (with difficulty) using the same technique as in patients.…”

The voltage dependence of Ih in human myelinated axons

“…The voltage‐gated inwardly rectifying current I h flows through hyperpolarization‐activated cyclic nucleotide‐gated (HCN) channels and plays an important role in pace‐making and determination of resting membrane potential (Pape, 1996; Biel et al 2009). Recent studies in vivo have suggested a contribution of I h to the determination of axonal threshold in human motor axons (Trevillion et al 2010) and to a number of pathologies including diabetes, stroke and porphyria (Horn et al 1996; Jankelowitz et al 2007; Lin et al 2008). HCN channels are of particular interest as molecular targets for neuropathic pain resulting from traumatic nerve damage or channelopathy (Chaplan et al 2003; Momin et al 2008; Momin & McNaughton, 2009; Wickenden et al 2009).…”

Evidence for Increased Glutamatergic Cortical Facilitation in Children and Adolescents With Major Depressive Disorder

“…31,32 The MT is influenced by voltage-gated sodium channels. 33 Prior work indicates that ICF indexes glutamatergic N-methyl-D-aspartate (NMDA) receptor functioning. This is supported by studies of NMDA antagonists that decrease ICF and studies in which the delay of excitatory postsynaptic potentials mediated by NMDA are consistent with the time interval of ICF.…”