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      Ionic Blockage of Sodium Channels in Nerve

      The Journal of General Physiology

      The Rockefeller University Press

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          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 ( pK a 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.

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          Author and article information

          Journal
          J Gen Physiol
          The Journal of General Physiology
          The Rockefeller University Press
          0022-1295
          1540-7748
          1 June 1973
          : 61
          : 6
          : 687-708
          Affiliations
          From the Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle, Washington 98195.
          Author notes

          Dr. Woodhull's present address is Hampshire College, Amherst, Massachusetts 01002.

          2203489
          4541078
          Copyright © 1973 by The Rockefeller University Press
          Categories
          Article

          Anatomy & Physiology

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