Modification of slow sodium inactivation in nerve after internal perfusion with trypsin.

Crayfish axons, internally perfused and held at depolarized membrane potentials, exhibit an inactivation of sodium conductance with slow kinetics. Restoration of maximum peak early currents requires prepulse hyperpolarizations of up to 1 s duration. Addition of trypsin to the internal perfusate at low concentrations (0.02 mg/ml) causes a rapid and irreversible loss of slow inactivation at the resting potential and a corresponding increase in Na currents to maximum values. After trypsin action, steady-state slow Na inactivation is shifted by 20--25 mV in the depolarizing direction, with no change in fast (h) inactivation. N-ethylmaleimide (NEM), a reagent with a high specificity for sulfhydryl groups, has been shown to induce slow inactivation, modify fast inactivation, and block a fraction of the Na conductance. After trypsin action NEM no longer increases slow Na inactivation but other effects remain. Prior exposure to NEM does not protect axons against the loss of slow inactivation caused by trypsin.