Skip to main content
PMC home page
The Journal of General Physiology logoLink to The Journal of General Physiology
. 1967 May 1;50(5):1413–1428. doi: 10.1085/jgp.50.5.1413

Comparison of Tetrodotoxin and Procaine in Internally Perfused Squid Giant Axons

Toshio Narahashi 1, Nels C Anderson 1, John W Moore 1
PMCID: PMC2225703  PMID: 6033593

Abstract

Squid giant axons were internally perfused with tetrodotoxin and procaine, and excitability and electrical properties were studied by means of current-clamp and sucrose-gap voltage-clamp methods. Internally perfused tetrodotoxin was virtually without effect on the resting potential, the action potential, the early transient membrane ionic current, and the late steady-state membrane ionic current even at very high concentrations (1,000–10,000 nM) for a long period of time (up to 36 min). Externally applied tetrodotoxin at a concentration of 100 nM blocked the action potential and the early transient current in 2–3 min. Internally perfused procaine at concentrations of 1–10 mM reversibly depressed or blocked the action potential with an accompanying hyperpolarization of 2–4 mv, and inhibited both the early transient and late steady-state currents to the same extent. The time to peak early transient current was increased. The present results and the insolubility of tetrodotoxin in lipids have led to the conclusion that the gate controlling the flow of sodium ions through channels is located on the outer surface of the nerve membrane.

Full Text

The Full Text of this article is available as a PDF (890.5 KB).

Selected References

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

  1. ARMSTRONG C. M., BINSTOCK L. ANOMALOUS RECTIFICATION IN THE SQUID GIANT AXON INJECTED WITH TETRAETHYLAMMONIUM CHLORIDE. J Gen Physiol. 1965 May;48:859–872. doi: 10.1085/jgp.48.5.859. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. BAKER P. F., HODGKIN A. L., SHAW T. I. Replacement of the protoplasm of a giant nerve fibre with artificial solutions. Nature. 1961 Jun 3;190:885–887. doi: 10.1038/190885a0. [DOI] [PubMed] [Google Scholar]
  3. BAKER P. F., HODGKIN A. L., SHAW T. I. The effects of changes in internal ionic concentrations on the electrical properties of perfused giant axons. J Physiol. 1962 Nov;164:355–374. doi: 10.1113/jphysiol.1962.sp007026. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Blaustein M. P., Goldman D. E. Competitive action of calcium and procaine on lobster axon. A study of the mechanism of action of certain local anesthetics. J Gen Physiol. 1966 May;49(5):1043–1063. doi: 10.1085/jgp.49.5.1043. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. DETTBARN W. D. The active form of local anesthetics. Biochim Biophys Acta. 1962 Feb 12;57:73–76. doi: 10.1016/0006-3002(62)91079-x. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. KOKETSU K., CERF J. A., NISHI S. Further observations on electrical activity of frog spinal ganglion cells in sodium-free solutions. J Neurophysiol. 1959 Nov;22:693–703. doi: 10.1152/jn.1959.22.6.693. [DOI] [PubMed] [Google Scholar]
  8. LARRAMENDI L. M., 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. doi: 10.1038/178316a0. [DOI] [PubMed] [Google Scholar]
  9. MOORE J. W., NARAHASHI T., ULBRICHT W. SODIUM CONDUCTANCE SHIFT IN AN AXON INTERNALLY PERFUSED WITH A SUCROSE AND LOW-POTASSIUM SOLUTION. J Physiol. 1964 Aug;172:163–173. doi: 10.1113/jphysiol.1964.sp007410. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. MOORE J. W., ULBRICHT W., TAKATA M. EFFECT OF ETHANOL ON THE SODIUM AND POTASSIUM CONDUCTANCES OF THE SQUID AXON MEMBRANE. J Gen Physiol. 1964 Nov;48:279–295. doi: 10.1085/jgp.48.2.279. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. MOSHER H. S., FUHRMAN F. A., BUCHWALD H. D., FISCHER H. G. TARICHATOXIN--TETRODOTOXIN: A POTENT NEUROTOXIN. Science. 1964 May 29;144(3622):1100–1110. doi: 10.1126/science.144.3622.1100. [DOI] [PubMed] [Google Scholar]
  12. Moore J. W., Blaustein M. P., Anderson N. C., Narahashi T. Basis of tetrodotoxin's selectivity in blockage of squid axons. J Gen Physiol. 1967 May;50(5):1401–1411. doi: 10.1085/jgp.50.5.1401. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. NAKAJIMA S., IWASAKI S., OBATA K. Delayed rectification and anomalous rectification in frog's skeletal muscle membrane. J Gen Physiol. 1962 Sep;46:97–115. doi: 10.1085/jgp.46.1.97. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. NARAHASHI T., DEGUCHI T., URAKAWA N., OHKUBO Y. Stabilization and rectification of muscle fiber membrane by tetrodotoxin. Am J Physiol. 1960 May;198:934–938. doi: 10.1152/ajplegacy.1960.198.5.934. [DOI] [PubMed] [Google Scholar]
  15. NARAHASHI T., MOORE J. W., SCOTT W. R. TETRODOTOXIN BLOCKAGE OF SODIUM CONDUCTANCE INCREASE IN LOBSTER GIANT AXONS. J Gen Physiol. 1964 May;47:965–974. doi: 10.1085/jgp.47.5.965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. NARAHASHI T. POTENTIAL, STRUCTURE, AND EXCITABILITY OF GIANT AXON MEMBRANE. J Gen Physiol. 1965 May;48:SUPPL–SUPPL:25. doi: 10.1085/jgp.48.5.19. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Nakamura Y., Nakajima S., Grundfest H. The action of tetrodotoxin on electrogenic components of squid giant axons. J Gen Physiol. 1965 Jul;48(6):975–996. [PubMed] [Google Scholar]
  18. OIKAWA T., SPYROPOULOS C. S., TASAKI I., TEORELL T. Methods for perfusing the giant axon of Loligo pealii. Acta Physiol Scand. 1961 Jun;52:195–196. doi: 10.1111/j.1748-1716.1961.tb02218.x. [DOI] [PubMed] [Google Scholar]
  19. PICKARD W. F., LETTVIN J. Y., MOORE J. W., TAKATA M., POOLER J., BERNSTEIN T. CAESUM IONS DO NOT PASS THE MEMBRANE OF THE GIANT AXON. Proc Natl Acad Sci U S A. 1964 Nov;52:1177–1183. doi: 10.1073/pnas.52.5.1177. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. ROSENBERG P., HIGMAN H. B., BARTELS E. The active structure of local anesthetics. Effects on electrical and cholinesterase activity. Biochim Biophys Acta. 1963 May 21;66:406–414. doi: 10.1016/0006-3002(63)91209-5. [DOI] [PubMed] [Google Scholar]
  21. SHANES A. M., FREYGANG W. H., GRUNDFEST H., AMATNIEK E. Anesthetic and calcium action in the voltage-clamped squid giant axon. J Gen Physiol. 1959 Mar 20;42(4):793–802. doi: 10.1085/jgp.42.4.793. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. TASAKI I., HAGIWAR A. S. Demonstration of two stable potential states in the squid giant axon under tetraethylammonium chloride. J Gen Physiol. 1957 Jul 20;40(6):859–885. doi: 10.1085/jgp.40.6.859. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. TASAKI I., TAKENAKA T. EFFECTS OF VARIOUS POTASSIUM SALTS AND PROTEASES UPON EXCITABILITY OF INTRACELLULARLY PERFUSED SQUID GIANT AXONS. Proc Natl Acad Sci U S A. 1964 Sep;52:804–810. doi: 10.1073/pnas.52.3.804. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. TASAKII, WATANABE A., TAKENAKA T. Resting and action potential of intracellularly perfused squid giant axon. Proc Natl Acad Sci U S A. 1962 Jul 15;48:1177–1184. doi: 10.1073/pnas.48.7.1177. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. TAYLOR R. E. Effect of procaine on electrical properties of squid axon membrane. Am J Physiol. 1959 May;196(5):1071–1078. doi: 10.1152/ajplegacy.1959.196.5.1071. [DOI] [PubMed] [Google Scholar]
  26. Takata M., Moore J. W., Kao C. Y., Fuhrman F. A. Blockage of sodium conductance increase in lobster giant axon by tarichatoxin (tetrodotoxin). J Gen Physiol. 1966 May;49(5):977–988. doi: 10.1085/jgp.49.5.977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. 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. doi: 10.1073/pnas.54.3.763. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES