Effects of some chemical reagents on sodium current inactivation in myelinated nerve fibers of the frog

The effect of several chemical reagents on the sodium current was studied in voltage-clamped single nerve fibers of the frog. The oxidants halazone and hypochlorous acid drastically inhibited inactivation. Their effect was similar to that of chloramine T (Wang, 1984a). The curve relating the steady-state inactivation parameter h infinity to the conditioning potential E became nonmonotonic after treatment with the oxidants, i.e., dh infinity/dE greater than 0 for E greater than -20 mV. By contrast, the oxidants periodate, iodate, and hydrogen peroxide (applied for the same time, but at higher concentrations) merely produced a parallel shift of the h infinity(E) curve to more negative values of membrane potential. Diethylpyrocarbonate, a reagent that preferentially modifies histidine groups, had one marked effect: a strong shift of the h infinity(E) curve to more negative values of membrane potential. Almost no effect was observed after application of the tyrosine-reactive reagent N-acetylimidazole. Similarly, the arginine-reactive reagent glyoxal had only minor effects on the Na permeability. The results suggest that methionine is not critically involved in the kinetics of Na current inactivation. Similarly, an essential tyrosine or arginine residue seems to be unavailable to chemical reagents from outside on the frog node of Ranvier. Deduced from the reactivities of (some of) the reagents used, modification of membrane lipids is a tentative explanation for the effects observed on inactivation kinetics.