The present study was undertaken to determine if the axonal hyperpolarization produced by a brief train of impulses would impair neural transmission in cutaneous afferents of normal human subjects (n = 25). To assess changes in axonal excitability, a submaximal test stimulus was conditioned by a train of 10 supramaximal stimuli at 200 Hz. This produced a depression in excitability lasting lip to 100 ms, demonstrable at nodes of Ranvier remote from the sire of stimulus application, and probably due to activation of a slow K+ conductance. The effects of this change in excitability on neural transmission were assessed using a supramaximal test pulse. This revealed small but significant activity-dependent deer-eases in amplitude at conditioning-test intervals lip to 20 ms and increases in latency at intervals up to 70 ms. Both the amplitude decrease and the latency increase were greater the longer the conduction distance. The reduction in amplitude of the compound sensory potential could be explained by temporal dispersion due to the increase in latency. It is concluded that, at the nodes of normal cutaneous afferents, the safety margin for impulse generation is sufficiently high that rite activity-dependent hyperpolarization does not produce conduction block. It is likely that the previously described reductions in the amplitude of the compound sensory action potential in response to brief trains of stimuli were due to dispersion of the volley, not conduction failure, and that conduction failure does not occur in normal cutaneous axons solely by activation of slow Kf conductances. It remains to be seen whether conduction block would occur due to this 'normal' physiological mechanism, when the safety margin is normally low (at, for example, a branch point) or is impaired by pathology (such as a focal neuropathy).
