On the Voltage-dependent Action of Tetrodotoxin

Overview

Journal Biophys J

Publisher Cell Press

Specialty Biophysics

Date 1977 Mar 1

PMID 843585

Citations 20

Authors

I S Cohen

G R Strichartz

Affiliations

Soon will be listed here.

Abstract

The use of the maximum rate-of-rise of the action potential (Vmax) as a measure of the sodium conductance in excitable membranes is invalid. In the case of membrane action potentials, Vmax depends on the total ionic current across the membrane; drugs or conditions that alter the potassium or leak conductances will also affect Vmax. Likewise, long-term depolarization of the membrane lessens the fraction of total ionic current that passes through the sodium channels by increasing potassium conductance and inactivating the sodium conductance, and thereby reduces the effect of Vmax of drugs that specifically block sodium channels. The resultant artifact, an apparent voltage-dependent potency of such drugs, is theoretically simulated for the effects of tetrodotoxin on the Hodgkin-Huxley squid axon.

Citing Articles

Ephaptic Coupling Is a Mechanism of Conduction Reserve During Reduced Gap Junction Coupling.

Lin J, Abraham A, George S, Greer-Short A, Blair G, Moreno A Front Physiol. 2022; 13:848019.

PMID: 35600295 PMC: 9117633. DOI: 10.3389/fphys.2022.848019.

Modulation of sodium channels as pharmacological tool for pain therapy-highlights and gaps.

Foadi N Naunyn Schmiedebergs Arch Pharmacol. 2018; 391(5):481-488.

PMID: 29572558 DOI: 10.1007/s00210-018-1487-3.

The intracellular sodium activity of sheep heart Purkinje fibres: effects of local anaesthetics and tetrodotoxin.

Deitmer J, Ellis D J Physiol. 1980; 300:269-82.

PMID: 7381786 PMC: 1279354. DOI: 10.1113/jphysiol.1980.sp013161.

Electrophysiological profile of the antiarrhythmic compound asocainol studied on perfused guinea-pig hearts and on isolated cardiac preparations.

Langenfeld H, Haverkampf K, ANTONI H Naunyn Schmiedebergs Arch Pharmacol. 1984; 326(2):155-62.

PMID: 6472493 DOI: 10.1007/BF00517313.

Use-dependent block of cardiac sodium channels by quaternary derivatives of lidocaine.

Gintant G, Hoffman B Pflugers Arch. 1984; 400(2):121-9.

PMID: 6326044 DOI: 10.1007/BF00585029.

References

Taylor R . Effect of procaine on electrical properties of squid axon membrane. Am J Physiol. 1959; 196(5):1071-8. DOI: 10.1152/ajplegacy.1959.196.5.1071. View

FRANKENHAEUSER B, HODGKIN A . The action of calcium on the electrical properties of squid axons. J Physiol. 1957; 137(2):218-44. PMC: 1362975. DOI: 10.1113/jphysiol.1957.sp005808. View

HODGKIN A, HUXLEY A . A quantitative description of membrane current and its application to conduction and excitation in nerve. J Physiol. 1952; 117(4):500-44. PMC: 1392413. DOI: 10.1113/jphysiol.1952.sp004764. View

Strichartz G . Molecular mechanisms of nerve block by local anesthetics. Anesthesiology. 1976; 45(4):421-41. DOI: 10.1097/00000542-197610000-00012. View

Harris J, Marshall M . Tetrodotoxin-resistant action potentials in newborn rat muscle. Nat New Biol. 1973; 243(127):191-2. DOI: 10.1038/newbio243191a0. View

Henderson R, Ritchie J, Strichartz G . The binding of labelled saxitoxin to the sodium channels in nerve membranes. J Physiol. 1973; 235(3):783-804. PMC: 1350793. DOI: 10.1113/jphysiol.1973.sp010417. View

Hille B . The receptor for tetrodotoxin and saxitoxin. A structural hypothesis. Biophys J. 1975; 15(6):615-9. PMC: 1334742. DOI: 10.1016/S0006-3495(75)85842-5. View

Harris J, THESLEFF S . Studies on tetrodotoxin resistant action potentials in denervated skeletal muscle. Acta Physiol Scand. 1971; 83(3):382-8. DOI: 10.1111/j.1748-1716.1971.tb05091.x. View

Hille B . Charges and potentials at the nerve surface. Divalent ions and pH. J Gen Physiol. 1968; 51(2):221-36. PMC: 2201126. DOI: 10.1085/jgp.51.2.221. View

10.

Hille B . Pharmacological modifications of the sodium channels of frog nerve. J Gen Physiol. 1968; 51(2):199-219. PMC: 2201123. DOI: 10.1085/jgp.51.2.199. View

11.

Kao C, FUHRMAN F . Differentiation of the actions of tetrodotoxin and saxitoxin. Toxicon. 1967; 5(1):25-34. DOI: 10.1016/0041-0101(67)90114-6. View

12.

Cahalan M . Modification of sodium channel gating in frog myelinated nerve fibres by Centruroides sculpturatus scorpion venom. J Physiol. 1975; 244(2):511-34. PMC: 1330774. DOI: 10.1113/jphysiol.1975.sp010810. View

13.

ULBRICHT W, Wagner H . The influence of pH on equilibrium effects of tetrodotoxin on myelinated nerve fibres of Rana esculenta. J Physiol. 1975; 252(1):159-84. PMC: 1348473. DOI: 10.1113/jphysiol.1975.sp011139. View

14.

Evans M . Tetrodotoxin, saxitoxin, and related substances: their applications in neurobiology. Int Rev Neurobiol. 1972; 15:83-166. DOI: 10.1016/s0074-7742(08)60329-3. View

15.

Hille B, Woodhull A, Shapiro B . Negative surface charge near sodium channels of nerve: divalent ions, monovalent ions, and pH. Philos Trans R Soc Lond B Biol Sci. 1975; 270(908):301-18. DOI: 10.1098/rstb.1975.0011. View

16.

Albuquerque E, Daly J, WITKOP B . Batrachotoxin: chemistry and pharmacology. Science. 1971; 172(3987):995-1002. DOI: 10.1126/science.172.3987.995. View

17.

Hagiwara S . Ca spike. Adv Biophys. 1973; 4:71-102. View

18.

Woodhull A . Ionic blockage of sodium channels in nerve. J Gen Physiol. 1973; 61(6):687-708. PMC: 2203489. DOI: 10.1085/jgp.61.6.687. View

19.

Henderson R, Ritchie J, Strichartz G . Evidence that tetrodotoxin and saxitoxin act at a metal cation binding site in the sodium channels of nerve membrane. Proc Natl Acad Sci U S A. 1974; 71(10):3936-40. PMC: 434301. DOI: 10.1073/pnas.71.10.3936. View

20.

Seyama I, Narahashi T . Increase in sodium permeability of squid axon membranes by -dihydrograyanotoxin II. J Pharmacol Exp Ther. 1973; 184(2):299-307. View