Variations in excitability of single human motor axons, related to stochastic properties of nodal sodium channels

Threshold variability of single human motor axons was studied by delivering 0.1 ms constant current stimuli of randomly varied intensity over the ulnar nerve at the elbow, and recording all‐or‐none potentials from flexor carpi ulnaris. In nine normal subjects, a single unit was tested with 8–11 000 stimuli at intervals of 0.5 s. After allowing for slow changes in excitability, the probability of excitation was in all cases well fitted by a cumulative Gaussian function. The relative spread (RS) of thresholds (s.d./mean) averaged 1.65 ± 0.26% (mean ±s.d., n= 9). When threshold was tested 20 ms after the start of a polarizing current, RS increased on depolarization and decreased on hyperpolarization. The product RS × mean threshold also increased on depolarization, especially when threshold was reduced by more than 50%. When the mean was reduced by 90%, RS increased above 50% and the axon sometimes fired spontaneously. Threshold variability was simulated by a computer model of a single node of Ranvier, in which the variability arose because of the stochastic behaviour of nodal sodium channels. The observed values of RS, and potential dependence of RS, were well modelled by a node with 60 000 sodium channels, of which about 1% were modelled as persistent sodium channels. Threshold variations in the model at resting potential were not primarily due to fluctuations in the state of the node before the stimulus was delivered, but rather to the variable activation of channels by the stimulus pulse. On depolarization, however, current through (mainly persistent) sodium channels caused appreciable fluctuations in membrane potential, which increased RS and the probability of spontaneous firing.