The permeability of sodium channels to hydrogen ions in nerve fibres.
Ionic currents in the node of Ranvier bathed in Na-free acid solutions (pH 3.4-4.6) were measured under voltage clamp conditions. Small (less than 0.1 nA) inward currents were detected in Na-free solutions at pH less than 4.0, whereas only outward currents were observed in Na-free solutions at normal pH. These currents have kinetics and voltage dependence of activation similar to those of sodium currents at low pH. They were blocked by tetrodotoxin (TTX) and benzocaine. After pretreatment of the membrane with aconitine both inward and outward ionic currents in Na-free acid solutions acquired a kinetics and voltage dependence of activation similar to those of the currents in aconitine-modified sodium channels at low pH. TTX and benzocaine inhibited these currents. Inward currents in aconitine-treated membrane appeared at pH 4.6 and were about ten times as large as those in untreated membrane. Both inward and outward ionic currents in Na-free acid solutions were suggested to be through normal or aconitine-modified sodium channels. Experiments with various concentrations of substituting cations [tris(hydroxymethyl)aminomethane, tetraethylammonium, choline], Ca2+ and H+ in Na-free acid solutions showed that the inward currents in normal and aconitine-modified sodium channels were carried by hydrogen ions. Hydrogen to sodium permeability ratio was determined from reversal potential measurements. It equals to (mean +/- S.E.) 252 +/- 16 and 1182 +/- 74 for normal and aconitine-modified sodium channels, respectively. The data obtained can be explained on assumption that in sodium channel energetic barriers for H+ are much lower than those for Na+. H+, however, passes through the channel very slowly because of the low rate of its removal from the acid group in selectivity filter.
D000157:Aconitine / Q000494:pharmacology; D000818:Animals; D004553:Electric Conductivity; D006859:Hydrogen / Q000378:metabolism*; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D009412:Nerve Fibers / Q000378:metabolism*; D010539:Permeability; D011895:Rana ridibunda; D012964:Sodium / Q000378:metabolism*
D007473:Ion Channels; D006859:Hydrogen; D012964:Sodium; D000157:Aconitine