Sodium channel function and the excitability of human cutaneous afferents during ischaemia.

The changes in excitability of cutaneous afferents in the median nerve of healthy subjects were compared during 13 min of ischaemia and during 13 min continuous depolarizing DC. In addition, intermittent polarizing currents were used to compensate for or to accentuate the threshold change produced by ischaemia. Measurements were made alternately of the ischaemic (or current-induced) changes in threshold, refractoriness and, in some experiments, supernormality. The strength-duration time constant (tau(SD)) was calculated from the thresholds to test stimuli of different duration. During ischaemia for 13 min, the threshold decreased steadily by 34 % over the initial 8 min, reached a plateau and increased slightly over the final few minutes. However, with continuous depolarizing DC, the threshold decreased linearly with the applied current, by 55 % with strong current ramps. Intermittent injection of hyperpolarizing DC was used to compensate for the ischaemic threshold change, but the compensating current increased progressively and did not reach a plateau as had occurred with the ischaemic threshold change. During ischaemia, tau(SD) increased to a plateau, following the threshold more closely than the current required to compensate for threshold. Refractoriness, on the other hand, increased more steeply than the applied compensating current. There were similar discrepancies in the relationships of tau(SD) and refractoriness to supernormality. The smaller-than-expected threshold change during ischaemia could result from limitations on the change in excitability produced by ischaemic metabolites acting on the gating and/or permeability of Na(+) channels. Intermittent depolarizing DC was applied during the ischaemic depolarization to determine whether it would reduce or accentuate the discrepancies noted during ischaemia alone. The extent of the threshold change was greater than with ischaemia alone, and there was a greater change in tau(SD) and a proportionately smaller change in refractoriness. It is concluded that ischaemia produces factors that can block Na(+) channels and/or alter their gating. Without these processes, the ischaemic change in threshold would be much greater than that actually recorded, probably sufficient to produce prominent ectopic impulse activity.