Irreversible modification of sodium channel inactivation in toad myelinated nerve fibres by the oxidant chloramine‐T.

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Abstract
The effects of externally applied chloramine-T on the excitability of single toad myelinated nerve fibers was studied. Chloramine-T is a mild oxidant which reacts specifically with the cysteine and methionine residues of proteins. Chloramine-T prolongs the action potential of a single myelinated fiber by more than 1000-fold. This effect is concentration- and time-dependent; higher concentrations and longer incubation times increase prolongation. Under voltage-clamp conditions, Na channel inactivation is markedly inhibited by chloramine-T while Na channel activation remains normal. Prolonged depolarization of the membrane leads to a maintained Na current. The maintained Na currents show activation kinetics, dependence on membrane potential and reversal potentials which are similar to those of normal, inactivating Na currents in untreated fibers. Both the maintained and the peak Na currents are equally inhibited by tetrodotoxin. After partial removal of Na inactivation by brief exposures to chloramine-T, the voltage dependence of the steady-state Na current inactivation (h.infin.) is shifted in the depolarized direction by about 20 mV, even after correction for the noninactivating component contributed by the maintained current. The phenomena described here imply that cysteine or methionine residues are critical for the Na channel inactivation processes. The 2 different modifications of inactivation, its removal shown by the maintained current and the shift in the voltage-dependence of the remaining inactivable channels, reveal that at least 2 separate residues are modified by chloramine-T.