Logo of jgenphysiolHomeThe Rockefeller University PressEditorsContactInstructions for AuthorsThis issue
J Gen Physiol. 1971 Dec 1; 58(6): 599–619.
PMCID: PMC2226049

The Permeability of the Sodium Channel to Organic Cations in Myelinated Nerve


The relative permeability of sodium channels to 21 organic cations was studied in myelinated nerve fibers. Ionic currents under voltage-clamp conditions were measured in sodium-free solutions containing the test cation. The measured reversal potential and the Goldman equation were used to calculate relative permeabilities. The permeability sequence was: sodium ≈ hydroxylamine > hydrazine > ammonium ≈ formamidine ≈ guanidine ≈ hydroxyguanidine > aminoguanididine >> methylamine. The cations of the following compounds were not measurably permeant: N-methylhydroxylamine, methylhydrazine, methylamine, methylguanidine, acetamidine, dimethylamine, tetramethylammonium, tetraethylammonium, ethanolamine, choline, tris(hydroxymethyl)amino methane, imidazole, biguanide, and triaminoguanidine. Thus methyl and methylene groups render cations impermeant. The results can be explained on geometrical grounds by assuming that the sodium channel is an oxygen-lined pore about 3 A by 5 A in cross-section. One pair of oxygens is assumed to be an ionized carboxylic acid. Methyl and amino groups are wider than the 3 A width of the channel. Nevertheless, cations containing amino groups can slide through the channel by making hydrogen bonds to the oxygens. However, methyl groups, being unable to form hydrogen bonds, are too wide to pass through.

Full Text

The Full Text of this article is available as a PDF (1.2M).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Binstock L, Lecar H. Ammonium ion currents in the squid giant axon. J Gen Physiol. 1969 Mar;53(3):342–361. [PMC free article] [PubMed]
  • CHENG SC. Functional uptake of hydrazine by frog nerve in sodium-deficient Ringer's solution. Nature. 1962 Feb 17;193:691–692. [PubMed]
  • Chidambaram R, Balasubramanian R, Ramachandran GN. Potential functions for hydrogen bond interactions. I. A modified Lippincott-Schroeder potential function for NH, O interaction between peptide groups. Biochim Biophys Acta. 1970 Nov 17;221(2):182–195. [PubMed]
  • DODGE FA, 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. [PMC free article] [PubMed]
  • Drouin H, The R. The effect of reducing extracellular pH on the membrane currents of the ranvier node. Pflugers Arch. 1969;313(1):80–88. [PubMed]
  • FRANKENHAEUSER B. A method for recording resting and action potentials in the isolated myelinated nerve fibre of the frog. J Physiol. 1957 Mar 11;135(3):550–559. [PMC free article] [PubMed]
  • Hille B. The selective inhibition of delayed potassium currents in nerve by tetraethylammonium ion. J Gen Physiol. 1967 May;50(5):1287–1302. [PMC free article] [PubMed]
  • Hille B. Pharmacological modifications of the sodium channels of frog nerve. J Gen Physiol. 1968 Feb;51(2):199–219. [PMC free article] [PubMed]
  • Hille B. Charges and potentials at the nerve surface. Divalent ions and pH. J Gen Physiol. 1968 Feb;51(2):221–236. [PMC free article] [PubMed]
  • Hille B. The hydration of sodium ions crossing the nerve membrane. Proc Natl Acad Sci U S A. 1971 Feb;68(2):280–282. [PMC free article] [PubMed]
  • Hladky SB, Haydon DA. Discreteness of conductance change in bimolecular lipid membranes in the presence of certain antibiotics. Nature. 1970 Jan 31;225(5231):451–453. [PubMed]
  • HODGKIN AL, HUXLEY AF. Currents carried by sodium and potassium ions through the membrane of the giant axon of Loligo. J Physiol. 1952 Apr;116(4):449–472. [PMC free article] [PubMed]
  • HUXLEY AF, STAMPFLI R. Direct determination of membrane resting potential and action potential in single myelinated nerve fibers. J Physiol. 1951 Feb;112(3-4):476–495. [PMC free article] [PubMed]
  • Koketsu K, Nishi S. Effects of tetrodotoxin on the action potential in Na-free media. Life Sci. 1966 Dec;5(24):2341–2346. [PubMed]
  • LARRAMENDI LM, LORENTE DE NO R, VIDAL F. Restoration of sodium-deficient frog nerve fibres by an isotonic solution of guanidinium chloride. Nature. 1956 Aug 11;178(4528):316–317. [PubMed]
  • LORENTE DE NO R, VIDAL F, LARRAMENDI LM. Restoration of sodium-deficient frog nerve fibres by onium ions. Nature. 1957 Apr 6;179(4562):737–738. [PubMed]
  • MULLINS LJ. An analysis of conductance changes in squid axon. J Gen Physiol. 1959 May 20;42(5):1013–1035. [PMC free article] [PubMed]
  • MULLINS LJ. The macromolecular properties of excitable membranes. Ann N Y Acad Sci. 1961 Sep 6;94:390–404. [PubMed]
  • Nonner W. A new voltage clamp method for Ranvier nodes. Pflugers Arch. 1969;309(2):176–192. [PubMed]
  • TASAKI I. New measurements of the capacity and the resistance of the myelin sheath and the nodal membrane of the isolated frog nerve fiber. Am J Physiol. 1955 Jun;181(3):639–650. [PubMed]
  • Tasaki I, Singer I. Membrane macromolecules and nerve excitability: a physico-chemical interpretation of excitation in squid giant axons. Ann N Y Acad Sci. 1966 Jul 14;137(2):792–806. [PubMed]
  • Tasaki I, Singer I, Watanabe A. Excitation of internally perfused squid giant axons in sodium-free media. Proc Natl Acad Sci U S A. 1965 Sep;54(3):763–769. [PMC free article] [PubMed]
  • Tasaki I, Singer I, Watanabe A. Excitation of squid giant axons in sodium-free external media. Am J Physiol. 1966 Sep;211(3):746–754. [PubMed]
  • TASAKI I, SPYROPOULOS CS. Permeability of the squid axon membrane to several organic molecules. Am J Physiol. 1961 Sep;201:413–419. [PubMed]
  • Urry DW. The gramicidin A transmembrane channel: a proposed pi(L,D) helix. Proc Natl Acad Sci U S A. 1971 Mar;68(3):672–676. [PMC free article] [PubMed]
  • Urry DW, Goodall MC, Glickson JD, Mayers DF. The gramicidin A transmembrane channel: characteristics of head-to-head dimerized (L,D) helices. Proc Natl Acad Sci U S A. 1971 Aug;68(8):1907–1911. [PMC free article] [PubMed]

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


Save items

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Compound
    PubChem chemical compound records that cite the current articles. These references are taken from those provided on submitted PubChem chemical substance records. Multiple substance records may contribute to the PubChem compound record.
  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem chemical substance records that cite the current articles. These references are taken from those provided on submitted PubChem chemical substance records.

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...