Three functions of sodium channels in the toad node of Ranvier are altered by trimethyloxonium ions

Voltage-clamped nodes of Ranvier of the toad Xenopus laevis were treated with trimethyloxonium ions (TMO) which are known to methylate carboxyl groups. TMO did not affect potassium channels but the sodium system was modified in three ways: a) the current was reduced, b) channels were rendered insensitive to tetrodotoxin (TTX) and c) the inactivation of all channels, TTX-resistant or not, was slowed in a potential range between 50 and 110 mV. Steady-state inactivation, however, was not changed. Presence of 100 nM TTX during TMO treatment prevented the production of TTX-resistant channels but did not hinder current reduction and slowing of inactivation. The TTX-resistant sodium channels were blocked by protons and had normal relative permeabilities to alkali metal ions. Repeated application of TMO further decreased the current and increased the relative amount of TTX-resistant channels; the slowing of inactivation, however, was quantitatively terminated after the first TMO treatment. It is concluded that the sodium channel contains at least three TMO-modifiable groups, which probably are carboxyl groups.