Skip to main content
Article thumbnail
Location of Repository

Ionic Blockage of Sodium Channels in Nerve

By Ann M. Woodhull

Abstract

Increasing the hydrogen ion concentration of the bathing medium reversibly depresses the sodium permeability of voltage-clamped frog nerves. The depression depends on membrane voltage: changing from pH 7 to pH 5 causes a 60% reduction in sodium permeability at +20 mV, but only a 20% reduction at +180 mV. This voltage-dependent block of sodium channels by hydrogen ions is explained by assuming that hydrogen ions enter the open sodium channel and bind there, preventing sodium ion passage. The voltage dependence arises because the binding site is assumed to lie far enough across the membrane for bound ions to be affected by part of the potential difference across the membrane. Equations are derived for the general case where the blocking ion enters the channel from either side of the membrane. For H+ ion blockage, a simpler model, in which H+ enters the channel only from the bathing medium, is found to be sufficient. The dissociation constant of H+ ions from the channel site, 3.9 x 10-6 M (pKa 5.4), is like that of a carboxylic acid. From the voltage dependence of the block, this acid site is about one-quarter of the way across the membrane potential from the outside. In addition to blocking as described by the model, hydrogen ions also shift the responses of sodium channel "gates" to voltage, probably by altering the surface potential of the nerve. Evidence for voltage-dependent blockage by calcium ions is also presented

Topics: Article
Publisher: The Rockefeller University Press
OAI identifier: oai:pubmedcentral.nih.gov:2203489
Provided by: PubMed Central
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • http://www.pubmedcentral.nih.g... (external link)
  • Suggested articles

    Citations

    1. (1964). A molecular structural basis for the excitation properties of axons.
    2. (1952). A quantitative description of membrane current and its application to conduction and excitation in nerve.
    3. (1968). Charges and potentials at the nerve surface. Divalent ions and pH.
    4. (1972). Current-voltage curves of porous membranes in the presence of pore-blocking ions. I. Narrow pores containing no more than one moving ion.
    5. (1972). Effect of external pH on the sodium currents in the squid giant axon.
    6. (1971). Effect of external pH upon the voltage-dependent currents of the squid giant axon.
    7. (1969). Effects of tetrodotoxin and tetraethylammonium chloride on the inside of the nodal membrane of Xenopus laevis. Pfluegers Arch.
    8. (1971). Evidence against hydrogen-calcium competition model for activation of electrically excitable membranes.
    9. (1971). Eyring rate theory model of the current-voltage relationships of ion channels in excitable membranes. In Chemical Dynamics: Papers in Honor of Henry Eyring.
    10. (1972). Intracellular pH electrode experiments on the giant squid axon.
    11. (1971). Ion transport through nerve membranes. Doctoral dissertation.
    12. (1972). Ionic blockage of sodium permeability in voltage clamped frog nerve. Doctoral dissertation.
    13. (1961). Kinetics and Mechanism.
    14. (1958). Membrane currents in isolated frog nerve fibre under voltage clamp conditions.
    15. (1963). Modern Chemical Kinetics.
    16. (1971). Molecular mechanisms of membrane ionic permeability changes.
    17. (1943). Potential, impedance, and rectification in membranes.
    18. (1964). Restoration of action potential by anodal polarization in lobster giant axons.
    19. (1959). Sodium currents in the myelinated nerve fibre of Xenopus laevis investigated with the voltage clamp technique.
    20. (1957). The action of calcium on the electrical properties of squid axons.
    21. (1969). The effect of reducing extracellular pH on the membrane currents of the Ranvier node. Pfluegers Arch.
    22. (1949). The effect of sodium ions on the electrical activity of the giant axon of the squid.
    23. (1969). The effects of external potassium and long duration voltage conditioning on the amplitude of sodium currents in the giant axon of the squid, Loligo pealei.
    24. (1972). The inner quaternary ammonium ion receptor in potassium channels of the node of Ranvier.
    25. (1972). The permeability of the sodium channel to metal cations in myelinated nerve.
    26. (1971). The permeability of the sodium channel to organic cations in myelinated nerve.
    27. (1967). The selective inhibition of delayed potassium currents in nerve by tetraethylammonium ion.

    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.