Activity-dependent hyperpolarization of human motor axons produced by natural activity

Abstract

1. The changes in excitability of motor axons produced by natural activity were measured in six healthy subjects using voluntary contractions lasting 15 s, 30 s and 1 min, by recording the changes in stimulus current required to produce a compound muscle action potential of approximately 60 % of maximum. 2. On cessation of the contractions there was a prominent increase in the current required to produce the target potential, accompanied by an increase in rheobase, a decrease in strength-duration time constant, and an increase in axonal supernormality. These changes indicate that the hypoexcitability was due to axonal hyperpolarization. 3. The activity-dependent hypoexcitability increased in depth and duration the longer the contraction. Following a 1 min contraction, it produced a 24 % increase in threshold, waning over 15 min. The hypoexcitability was greater than in cutaneous afferents tetanized to produce an equivalent rate-dependent stress. 4. It is concluded that natural activity results in substantial hyperpolarization of active axons and that, for similar discharge rates, the degree of hyperpolarization is greater in motor axons than cutaneous afferents. The greater effect of activity on the excitability of motor axons could be due to less inward rectification and less persistent Na+ conductance than in sensory axons. It is suggested that motor axons may therefore be more susceptible than cutaneous afferents to conduction block at sites of impaired safety margin for impulse conduction.

Figure 1. Changes in excitability in a single subject

The median nerve was stimulated at the wrist and a 70% CMAP was tracked over the thenar muscles, using increments and decrements in stimulus intensity of 2%. At 5 min, a 60 s voluntary contraction was performed by the subject. A, threshold changes measured using test stimuli of 1.0 and 0.1 ms duration, normalized to 1.0. B, threshold changes during the supernormal period measured using a 0.1 ms test stimulus, delivered 7 ms after a supramaximal conditioning stimulus. Supernormality is expressed as the decrease in current below the control threshold necessary to produce the target CMAP. C, strength-duration time constant, calculated from the threshold changes in A.

Figure 2. Changes in excitability indices following contraction for 1 min

Post-contraction changes in threshold (A), supernormality (B), rheobase (C), and time constant (D). C and D were calculated using the 0.1 ms and 1.0 ms data from A. All data points represent mean ± s.e.m. for six subjects. For this figure, five consecutive data points were averaged.

Figure 3. Dependence of the decrease in excitability on the duration of contraction

Threshold changes, measured using 1.0 and 0.1 ms test stimuli (^, continuous line, respectively), for contractions lasting 15, 30 and 60 s. Each trace represents mean data for six subjects. The data in C are the same as in Fig. 2A, but without the smoothing created by averaging consecutive data points.

Figure 4. Activity-dependent changes in threshold for motor axons and cutaneous afferents in three subjects

A, mean threshold change following a 60 s voluntary contraction of the thenar muscles. B and C, mean changes in threshold of cutaneous afferents after tetanic stimulation at 20 Hz for 60 s (B) and at 50 Hz for 60 s (C). D, comparison of the threshold change for motor axons (from A) with that for cutaneous afferents following the 50 Hz tetanic train (from C). Error bars represent ± s.e.m.