Excitability and the safety margin in human axons during hyperthermia.

Abstract  Hyperthermia challenges the nervous system's ability to transmit action potentials faithfully. Neuromuscular diseases, particularly those involving demyelination have an impaired safety margin for action potential generation and propagation, and symptoms are commonly accentuated by increases in temperature. The aim of this study was to examine the mechanisms responsible for reduced excitability during hyperthermia.

The voltage dependence of I(h) in human myelinated axons.

HCN channels are responsible for I(h), a voltage-gated inwardly rectifying current activated by hyperpolarization. This current appears to be more active in human sensory axons than motor and may play a role in the determination of threshold. Differences in I(h) are likely to be responsible for the high variability in accommodation to hyperpolarization seen in different subjects.

Properties of low-threshold motor axons in the human median nerve.

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.

Threshold behaviour of human axons explored using subthreshold perturbations to membrane potential.

The present study explores the threshold behaviour of human axons and the mechanisms contributing to this behaviour. The changes in excitability of cutaneous afferents in the median nerve at the wrist were recorded to a long-lasting subthreshold conditioning stimulus, with a waveform designed to maximize the contribution of currents active in the just-subthreshold region. The conditioning stimulus produced a decrease in threshold that developed over 3-5 ms following the end of the depolarization and then decayed slowly, in a pattern similar to the recovery of axonal excitability following a discharge.

Inflections in threshold electrotonus to depolarizing currents in sensory axons.

Threshold electrotonus involves tracking the changes in axonal excitability produced by subthreshold polarizing currents and is the only technique that allows insight into the function of internodal conductances in human subjects in vivo. There is often an abrupt transient reversal of the threshold change as excitability increases in response to conditioning depolarizing currents (S1 phase). In recordings from motor axons, it has been recently demonstrated that this notch or inflection is due to activation of low-threshold axons.

Outwardly rectifying deflections in threshold electrotonus due to K+ conductances.

A transient decrease in excitability occurs regularly during the S1 phase of threshold electrotonus to depolarizing conditioning stimuli for sensory and, less frequently, motor axons. This has been attributed to the outwardly rectifying action of fast K(+) channels, at least in patients with demyelinating diseases. This study investigates the genesis of this notch in healthy axons.

Augmentation of the contraction force of human thenar muscles by and during brief discharge trains.

We investigated the influence of the history of activity on the contractile properties of abductor pollicis brevis (APB) to define how the forces produced by individual stimuli change within a stimulus train, with a view to clarifying the optimal discharge frequency for force production in brief trains. Supramaximal electrical stimuli were delivered to the median nerve at the wrist singly or in trains of 2-5 at various interstimulus intervals (ISIs). The force and electromyographic (EMG) responses to trains of n stimuli were defined by online subtraction of the responses to n - 1 stimuli.

Assessment of cortical excitability using threshold tracking techniques.

Conventional paired-pulse transcranial magnetic stimulation (TMS) techniques of assessing cortical excitability are limited by fluctuations in the motor evoked potential (MEP) amplitude. The aim of the present study was to determine the feasibility of threshold tracking TMS for assessing cortical excitability in a clinical setting and to establish normative data. Studies were undertaken in 26 healthy controls, tracking the MEP response from abductor pollicis brevis.

After-effects of near-threshold stimulation in single human motor axons.

Subthreshold electrical stimuli can generate a long-lasting increase in axonal excitability, superficially resembling the phase of superexcitability that follows a conditioning nerve impulse. This phenomenon of 'subthreshold superexcitability' has been investigated in single motor axons in six healthy human subjects, by tracking the excitability changes produced by conditioning stimuli of different amplitudes and waveforms. Near-threshold 1 ms stimuli caused a mean decrease in threshold at 5 ms of 22.

Axonal excitability measured by tracking twitch contraction force.

The present study addressed whether the excitability of motor axons could be documented by tracking a target submaximal contraction force rather than a target submaximal compound muscle action potential (CMAP). In 10 subjects, multiple excitability measures were recorded using the Trond protocol, tracking twitch contraction force and the CMAP in response to stimulation of the median nerve at the wrist and twitch force to stimulation at the motor point. With stimulation at the wrist, the findings were virtually identical with force tracking and CMAP tracking for indices dependent on unconditioned thresholds (stimulus-response curves; strength-duration properties) and when the conditioning stimulus was subthreshold (threshold electrotonus; current-threshold relationship).