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The permeability of sodium channels to hydrogen ions in nerve fibres

  • Excitable Tissues and Central Nervous Physiology
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Abstract

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<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.

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References

  • Århem P, Frankenhaeuser B (1974) Local anesthetics: Effect on permeability properties of nodal membrane in myelinated nerve fromXenopus laevis. Potential clamp experiments. Acta Physiol Scand 91:11–21

    Google Scholar 

  • Armstrong CM (1975) Ionic pores, gates and gating currents. Q Rev Biophys 7:179–210

    Google Scholar 

  • Begenisich T, Cahalan MD (1980) Sodium channel permeation in squid axons: I. Reversal potential experiments. J Physiol 307:217–242

    Google Scholar 

  • Binstock L (1976) Permeability of the sodium channel inMyxicola to organic cations. J Gen Physiol 68:551–562

    Google Scholar 

  • Carbone F, Fiorovanti R, Prestipino G, Wanke E (1978) Action of extracellular pH on Na and K membrane currents in the giant axon ofLoligo vulgaris. J Mem Biol 43:295–315

    Google Scholar 

  • Chandler WK, Meves H (1965) Voltage clamp experiments on internally perfused giant axons. J Physiol 180:788–860

    Google Scholar 

  • Chizmadjev Yu A, Khodorov BI, Aityan S Kh (1974) Analysis of the independence principle for the sodium channels of biological membranes. Bioelectrochem Bioenerg 1:301–312

    Google Scholar 

  • Drouin H, Neumcke B (1974) Specific and unspecific charges at the sodium channels of the nerve membrane. Pflügers Arch 351:207–229

    Google Scholar 

  • Hille B (1968) Charges and potentials at the nerve surface. Divalent ions and pH. J Gen Physiol 51:221–236

    Google Scholar 

  • Hille B (1971) The permeability of the sodium channel to organic cations in myelinated nerve. J Gen Physiol. 58:599–619

    Google Scholar 

  • Hille B (1972) The permeability of the sodium channel to metal cations in myelinated nerve. J Gen Physiol 59:637–658

    Google Scholar 

  • Hille B (1975a) An essential ionized acid group in sodium channels. Fed Proc 34:1318–1321

    Google Scholar 

  • Hille B (1975b) Ionic selectivity, saturation and block in sodium channels. A four-barrier model. J Gen Physiol 66:535–560

    Google Scholar 

  • Hille B (1977a) The pH-dependent rate of action of local anesthetics on the node of Ranvier. J Gen Physiol 69:475–496

    Google Scholar 

  • Hille B (1977b) Local anesthetics: hydrophilic and hydrophobic pathways for the drug-receptor reaction. J Gen Physiol 69:497–515

    Google Scholar 

  • Hille B, Woodhull AM, Shapiro BI (1975) Negative surface charge near sodium channels of nerve: divalent ions, monovalent ions, and pH. Phil Trans R Soc Lond B 270:301–318

    Google Scholar 

  • Hodgkin AL, Katz B (1949) The effect of sodium ions on the electrical activity of the giant axon of the squid. J Physiol 108:37–77

    Google Scholar 

  • Khodorov BI, Shishkova LD, Peganov EM, Revenko SV (1976) Inhibition of sodium currents in frog Ranvier node treated with local anesthetics. Role of slow sodium inactivation. Biochim Biophys Acta 433:409–435

    Google Scholar 

  • Khodorov BI, Guselnikova G, Peganov E (1979) Effect of benzocaine on the sodium gating currents in the membrane of myelinated nerve fibre. Dokl Akad Nauk SSSR 244:1252–1255 (in Russian)

    Google Scholar 

  • Krutetskaya ZI, Lonsky AV, Mozhayeva GN, Naumov AP (1978) Two-component nature of the asymmetrical displacement currents in the nerve membrane: the kinetic and pharmacological analysis. Tsitologia 20:1269–1277 (in Russian)

    Google Scholar 

  • Meyers VA, Haydon DA (1972) Ion transfer across lipid membranes in the presence of gramicidin A. II. The ion selectivity. Biochim Biophys Acta 274:313–322

    Google Scholar 

  • Mozhayeva GN, Naumov AP, Negulyaev Yu A (1976) Effect of aconitine on some properties of sodium channels in the Ranvier node membrane. Neurophysiologia 8:152–160 (in Russian)

    Google Scholar 

  • Mozhayeva GN, Naumov AP, Negulyaev Yu A, Nosyreva ED (1977) The permeability of aconitine-modified sodium channels to univalent cations. Biochim Biophys Acta 466:461–473

    Google Scholar 

  • Mozhayeva GN, Naumov AP, Negulyaev Yu A (1982) Evidence for existence of two acid groups controlling the conductance of sodium channel. Biochim Biophys Acta 643:251–255

    Google Scholar 

  • Mozhayeva GN, Naumov AP, Negulyaev Yu A (1982a) The interaction of H+ ions with acid groups in sodium channel. Gen Physiol Biophys (Bratislava) 1:5–19

    Google Scholar 

  • Mozhayeva GN, Naumov AP, Negulyaev Yu A (1982b) The interaction of H+ ions with acid groups in aconitine-modified sodium channel. Gen Physiol Biophys (Bratislava) 1:21–35

    Google Scholar 

  • Naumov AP, Negulyaev Yu A, Nosyreva ED (1979) Change in sodium channel acid group affinitiy for hydrogen ions under the action of aconitine. Dokl Akad Nauk SSSR 244:229–233 (in Russian)

    Google Scholar 

  • Negulyaev Yu A, Nosyreva ED (1979) A comparative study of procaine and benzocaine effect on normal and aconitine-modified sodium channels. Tsitologia 21:697–701 (in Russian)

    Google Scholar 

  • Neher E, Sandblom J, Eisenman G (1978) Ionic selectivity, saturation and block in gramicidin A channels. II. Saturation behavior on single channel conductances and evidence for existence of multiple binding sites in the channel. J Membr Biol 40:97–116

    Google Scholar 

  • Neumcke B, Nonner W, Stämpfli R (1976) Asymmetrical displacement current and its relation with activation of sodium current in the membrane of frog myelinated nerve. Pflügers Arch 363:193–203

    Google Scholar 

  • Neumcke B, Schwarz W, Stämpfli R (1980) Increased charge displacement in the membrane of myelinated nerve at reduced extracellular pH. Biophys J 31:325–332

    Google Scholar 

  • Neumcke B, Schwarz W, Stämpfli R (1981) Block of Na channels in the membrane of myelinated nerve by benzocaine. Pflügers Arch 390:230–236

    Google Scholar 

  • Robinson RA, Stokes RH (1959) Electrolyte solutions. Butterworth Scientific Publications, London, pp 120–121

    Google Scholar 

  • Schauf CL, Davis FA (1976) Sensitivity of the sodium channels ofMyxicola giant axons to changes in external pH. J Gen Physiol 67:185–196

    Google Scholar 

  • Schmidt H, Schmitt O (1974) Effect of aconitine on the sodium permeability of the node of Ranvier. Pflügers Arch 349:133–148

    Google Scholar 

  • Spalding BC (1978) Removal of TTX sensitivity in muscle fibres by trimethyloxonium ion: Two acid groups at the sodium channel. Biophys J 21:41a

    Google Scholar 

  • Spalding BC (1980) Properties of toxin-resistent sodium channels produced by chemical modification in frog sceletal muscle. J Physiol 305:485–500

    Google Scholar 

  • Ulbricht W, Wagner HH (1975) The influence of pH on equilibrium effects of tetrodotoxin on myelinated nerve fibres ofRana esculenta. J Physiol 252:159–184

    Google Scholar 

  • Wanke E, Carbone E, Testa PL (1980) The sodium channel and intracellular H+ blockage in squid axons. Nature 287:62–63

    Google Scholar 

  • Woodhull AM (1973) Ionic blockage of sodium channels in nerve. J Gen Physiol 61:687–708

    Google Scholar 

Download references

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Authors and Affiliations

  1. Institute of Cytology, Academy of Science of the USSR, Tikhoretsky Av. 4, 194064, Leningrad, USSR

    G. N. Mozhayeva & A. P. Naumov

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  1. G. N. Mozhayeva
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  2. A. P. Naumov
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Mozhayeva, G.N., Naumov, A.P. The permeability of sodium channels to hydrogen ions in nerve fibres. Pflugers Arch. 396, 163–173 (1983). https://doi.org/10.1007/BF00615521

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  • DOI: https://doi.org/10.1007/BF00615521

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