Differences in activity-dependent hyperpolarization in human sensory and motor axons

Abstract

The present study was undertaken to determine whether activity-dependent changes in axonal excitability are greater in motor axons than cutaneous afferents for the same impulse load. In nine healthy subjects, supramaximal stimulation at 8 Hz was delivered to the median nerve at the wrist. Changes in the threshold current required to generate compound motor and sensory potentials approximately 50% of maximum and other indices of axonal excitability were tracked before and after repetitive stimulation for 10 min. The long-lasting stimulation produced a prolonged depression in the excitability of both cutaneous afferents and motor axons, with gradual recovery to control levels over 15-20 min. These changes in threshold were associated with a reduction in refractoriness, an increase in supernormality and a decrease in the strength-duration time constant, changes consistent with axonal hyperpolarization. Greater changes in threshold occurred in motor axons: threshold increased by 9.9% and 16.4% for test stimulus durations of 0.1 and 1 ms, respectively, for motor axons and by 5.4% and 8.3% for cutaneous afferents. With higher stimulus frequencies and thereby greater impulse loads, greater threshold changes could be induced in cutaneous afferents. It is argued that the hyperpolarization resulted from activity of the electrogenic Na(+)-K+ pump, that it requires > 125 ms to restore the resting state following an action potential, and that significant intracellular Na+ accumulation occurs during a steady 8-Hz train. These findings imply that physiological discharge rates will activate the pump and thereby produce axonal hyperpolarization, the extent of which will vary with impulse load. A plausible explanation is that greater activity-dependent hyperpolarization in motor axons is due to less inward rectification as a result of less activity of the hyperpolarization-activated cation conductance (IH) than in cutaneous afferents.

Figure 1. Activity-dependent changes in threshold for motor and sensory axons

Mean changes in threshold (± s.e.m) recorded for 9 subjects following repetitive stimulation of the median nerve at the wrist at 8 Hz for 10 min. Changes are shown for motor (A) and sensory axons (B) using test stimuli of 0.1 and 1 ms duration. Immediately following cessation of impulse trains, axons became less excitable, with a prominent increase in threshold, significantly greater for motor axons when compared to sensory.

Figure 2. Comparison of changes in threshold and excitability indices for motor and sensory axons during and after repetitive stimulation

A, mean data (± s.e.m) for 9 subjects recorded following repetitive stimulation of the median nerve at the wrist at 8 Hz for 10 min. Threshold change for a 1.0 ms test stimulus normalized to resting levels for motor (•) and sensory (○) axons following repetitive stimulation. B and C, relative refractoriness and supernormality expressed as the change in threshold for the test potential as a percentage of the unconditioned threshold. D, τ_SD calculated off-line from the thresholds measured using test stimuli of 0.1 and 1 ms duration.

Figure 3. Relationships between normalized threshold and relative refractoriness, supernormality and τ_SD for motor and sensory axons following repetitive stimulation

Mean data from Fig. 2 are plotted against normalized threshold (from Fig. 2A) for relative refractoriness (A), supernormality (B) and τ_SD (C) for motor (•) and sensory (○) axons following repetitive activity.

Figure 4. The effects of impulse load on axonal excitability

Comparison of threshold changes for different rates of repetitive stimulation at 8 Hz, 20 Hz and 30 Hz in sensory axons with 8 Hz stimulation in motor axons for test stimulus durations of 0.1 ms (A) and 1.0 ms (B); peak threshold change again for test stimulus durations of 0.1 ms and 1.0 ms with data from Fig. 4A and B for motor at 8 Hz (black column) and sensory axons of progressive frequencies (C); and the cumulative threshold changes in area for 1 ms test stimuli from Fig. 4B (D).