Ischaemic changes in refractoriness of human cutaneous afferents under threshold-clamp conditions

1. A technique was developed to counteract the changes in threshold to elec trical stimuli of large myelinated cutaneous afferents in the human median nerve induced by ischaemia for 13 min. Intermittent application of polarizi ng currents was used in five subjects, in whom refractoriness, supernormali ty and the strength-duration time constant (tau(SD)) were tracked to determ ine whether compensating for the ischaemia-induced changes in threshold als o controlled the ischaemic changes in these excitability parameters. 2. The threshold compensation prevented the ischaemic changes in tau(SD), a n excitability parameter dependent on nodal Na+ channels. Threshold compens ation did not prevent the changes in refractoriness and supernormality, whe ther the compensation began 10, 100 or 200 ms prior to the test stimuli. 3. In three subjects, continuous polarizing current was injected for 13 min to compensate for the ischaemic change in threshold, thus clamping thresho ld at the pre-ischaemic level. Again, tau(SD) was effectively controlled, b ut there were still ischaemic changes in refractoriness and supernormality. 4. The effective control of tau(SD) suggests that both the intermittent thr eshold compensation and the continuous threshold damp effectively controlle d membrane potential at the node of Ranvier. 5. The ischaemic increase in refractoriness when threshold was kept constan t could be due to interference with the processes responsible for refractor iness by a metabolic product of ischaemia. The ischaemic change in supernor mality during effective compensation probably results from the intrusion of refractoriness into the conditioning-test intervals normally associated wi th maximal supernormality. 6. The present results indicate that ischaemia has effects on axonal excita bility that cannot be readily explained by changes in membrane potential. S pecifically, it is suggested that ischaemic metabolites interfere with the recovery of Na+ channels from inactivation.