Motoneuron afterhyperpolarisation duration in amyotrophic lateral sclerosis

Motor unit (MU) potentials were registered from 20 ALS patients and 13 age-matched control individuals during isometric constant force contractions of brachial biceps (BB). The registered signals were decomposed into single MU potential trains. The estimates of duration of the afterhyperpolarisation (AHP) in MNs, derived from the interspike interval variability, was compared between ALS patients (124 MNs) and control subjects (111 MNs) and no significant differences were encountered. However, the relationship between TI and age for patients appeared to be qualitatively different from that of the control group. The dependence of patients' AHPs on relative force deficit (RFD), which quantified muscle involvement, was more specific. For RFDs below 30%, the AHP estimate was significantly lower than control values and then increased thereafter with increasing RFDs. Moreover, firing rates of patients with the smallest RFDs were significantly higher while firing rates of patients with the greatest RFDs were significantly lower than control values. The AHP shortening in the early stages of muscle impairment is consistent with the decrease in firing threshold of ‘fast' MNs found in spinal cord slices from neonatal SOD1 mice. The later elongation of the AHP may be caused by the higher vulnerability of ‘fast' MNs to degeneration and by the influence of reinnervation. Our results are comparable to what has been observed in acute experiments in animal models, providing a bridge between animal and clinical research that may be relevant for identification of mechanism(s) underlying neurodegeneration in ALS.