Changes in excitability indices of cutaneous afferents produced by ischaemia in human subjects

1. The present study was undertaken to determine whether mechanisms other t han membrane depolarization contribute to the changes in excitability of cu taneous afferents of the median nerve under ischaemic conditions. 2. In six healthy subjects, axonal excitability was measured as the recipro cal of the threshold for a compound sensory action potential (CSAP) of 50 % maximal amplitude. Refractoriness and supernormality were measured as thre shold changes 2 and 7 ms, respectively, after supramaximal conditioning sti muli. The strength-duration time constant (tau(SD)) was calculated from the thresholds for unconditioned CSAPs using test stimuli of 0.1 and 1.0 ms du ration. Changes in these indices were measured when subthreshold polarizing currents lasting 10 or 100 ms were applied, before, during and after ischa emia for 13 min. 3. At rest, the change in supernormality produced by polarizing currents wa s greater with the longer polarizing current, indicating that it took up to 100 ms to charge the internodal capacitance. 4. Refractoriness and its dependence on excitability increased more than ex pected during ischaemia. Supernormality was abolished during ischaemia, and reached a maximum after ischaemia but was then barely altered by polarizin g current, tau(SD) had a similar relationship to excitability before, durin g and after ischaemia. 5. By contrast, during continuous depolarizing current for 8 min to mimic t he depolarization produced by ischaemia, the relationship between excitabil ity and refractoriness was the same during the depolarization as before it. 6. It is suggested that the large increase in refractoriness during ischaem ia might be due to interference with the recovery from inactivation of tran sient sodium channels by an intraaxonal substrate of ischaemia. The post-is chaemic increase in supernormality and the lack of change with changes in a xonal excitability can be explained by blockage of voltage-dependent potass ium channels.