Skip to main content
NCBI home page
The Journal of General Physiology logoLink to The Journal of General Physiology
. 1973 Jun 1;61(6):687–708. doi: 10.1085/jgp.61.6.687

Ionic Blockage of Sodium Channels in Nerve

Ann M Woodhull 1
PMCID: PMC2203489  PMID: 4541078

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.

Full Text

The Full Text of this article is available as a PDF (1.3 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adelman W. J., Jr, Palti Y. 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. J Gen Physiol. 1969 Nov;54(5):589–606. doi: 10.1085/jgp.54.5.589. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Armstrong C. M., Hille B. The inner quaternary ammonium ion receptor in potassium channels of the node of Ranvier. J Gen Physiol. 1972 Apr;59(4):388–400. doi: 10.1085/jgp.59.4.388. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Baker P. F., Hodgkin A. L., Ridgway E. B. Depolarization and calcium entry in squid giant axons. J Physiol. 1971 Nov;218(3):709–755. doi: 10.1113/jphysiol.1971.sp009641. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bicher H. I., Oki S. Intracellular pH electrode. Experiments on the giant squid axon. Biochim Biophys Acta. 1972 Mar 17;255(3):900–904. doi: 10.1016/0005-2736(72)90401-4. [DOI] [PubMed] [Google Scholar]
  5. DODGE F. A., FRANKENHAEUSER B. Membrane currents in isolated frog nerve fibre under voltage clamp conditions. J Physiol. 1958 Aug 29;143(1):76–90. doi: 10.1113/jphysiol.1958.sp006045. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. DODGE F. A., FRANKENHAEUSER B. Sodium currents in the myelinated nerve fibre of Xenopus laevis investigated with the voltage clamp technique. J Physiol. 1959 Oct;148:188–200. doi: 10.1113/jphysiol.1959.sp006281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Ehrenstein G., Fishman H. M. Evidence against hydrogen-calcium competition model for activation of electrically excitable membranes. Nat New Biol. 1971 Sep 1;233(35):16–17. doi: 10.1038/newbio233016a0. [DOI] [PubMed] [Google Scholar]
  8. FRANKENHAEUSER B., HODGKIN A. L. The action of calcium on the electrical properties of squid axons. J Physiol. 1957 Jul 11;137(2):218–244. doi: 10.1113/jphysiol.1957.sp005808. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Fishman S. N., Chodorov B. I., Volkenstein M. V. Molecular mechanisms of membrane ionic permeability changes. Biochim Biophys Acta. 1971 Jan 5;225(1):1–10. doi: 10.1016/0005-2736(71)90277-x. [DOI] [PubMed] [Google Scholar]
  10. GOLDMANN D. E. A MOLECULAR STRUCTURAL BASIS FOR THE EXCITATION PROPERTIES OF AXONS. Biophys J. 1964 May;4:167–188. doi: 10.1016/s0006-3495(64)86776-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. HODGKIN A. L., HUXLEY A. F. A quantitative description of membrane current and its application to conduction and excitation in nerve. J Physiol. 1952 Aug;117(4):500–544. doi: 10.1113/jphysiol.1952.sp004764. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. HODGKIN A. L., KATZ B. The effect of sodium ions on the electrical activity of giant axon of the squid. J Physiol. 1949 Mar 1;108(1):37–77. doi: 10.1113/jphysiol.1949.sp004310. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Heckmann K., Lindemann B., Schnakenberg J. Current-voltage curves of porous membranes in the presence of pore-blocking ions. I. Narrow pores containing no more than one moving ion. Biophys J. 1972 Jun;12(6):683–702. doi: 10.1016/S0006-3495(72)86112-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hille B. Charges and potentials at the nerve surface. Divalent ions and pH. J Gen Physiol. 1968 Feb;51(2):221–236. doi: 10.1085/jgp.51.2.221. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hille B. The permeability of the sodium channel to metal cations in myelinated nerve. J Gen Physiol. 1972 Jun;59(6):637–658. doi: 10.1085/jgp.59.6.637. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hille B. The permeability of the sodium channel to organic cations in myelinated nerve. J Gen Physiol. 1971 Dec;58(6):599–619. doi: 10.1085/jgp.58.6.599. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hille B. The selective inhibition of delayed potassium currents in nerve by tetraethylammonium ion. J Gen Physiol. 1967 May;50(5):1287–1302. doi: 10.1085/jgp.50.5.1287. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Koppenhöfer E., Vogel W. Wirkung von Tetrodotoxin und Tetraäthylammoniumchlorid an der Innenseite der Schnürringsmembran von Xenopus laevis. Pflugers Arch. 1969;313(4):361–380. doi: 10.1007/BF00593959. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of General Physiology are provided here courtesy of The Rockefeller University Press

RESOURCES