Abstract
Voltage clamp measurements on myelinated nerve fibers show that tetrodotoxin, saxitoxin, and DDT specifically affect the sodium channels of the membrane. Tetrodotoxin and saxitoxin render the sodium channels impermeable to Na ions and to Li ions and probably prevent the opening of individual sodium channels when one toxin molecule binds to a channel. The apparent dissociation constant of the inhibitory complex is about 1 nM for the cationic forms of both toxins. The zwitter ionic forms are much less potent. On the other hand, DDT causes a fraction of the sodium channels that open during a depolarization to remain open for a longer time than is normal. The effect cannot be described as a specific change in sodium inactivation or as a specific change in sodium activation, for both processes continue to govern the opening of the sodium channels and neither process is able to close the channels. The effects of DDT are very similar to those of veratrine.
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.
- Camougis G., Takman B. H., Tasse J. R. Potency difference between the zwitterion form and the cation forms of tetrodotoxin. Science. 1967 Jun 23;156(3782):1625–1627. doi: 10.1126/science.156.3782.1625. [DOI] [PubMed] [Google Scholar]
- DEL CASTILLO J., STARK L. Local responses in single medullated nerve fibres. J Physiol. 1952 Oct;118(2):207–215. doi: 10.1113/jphysiol.1952.sp004787. [DOI] [PMC free article] [PubMed] [Google Scholar]
- DETTBARN W. D., HIGMAN H. B., BARTELS E., PODLESKI T. EFFECTS OF MARINE TOXINS ON ELECTRICAL ACTIVITY AND K+ EFFLUX OF EXCITABLE MEMBRANES. Biochim Biophys Acta. 1965 Mar 29;94:472–478. doi: 10.1016/0926-6585(65)90055-5. [DOI] [PubMed] [Google Scholar]
- Goto T., Kishi Y., Takahashi S., Hirata Y. Tetrodotoxin. Tetrahedron. 1965 Aug;21(8):2059–2088. doi: 10.1016/s0040-4020(01)98344-9. [DOI] [PubMed] [Google Scholar]
- 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]
- KAO C. Y., FUHRMAN F. A. Pharmacological studies on tarichatoxin, a potent neurotoxin. J Pharmacol Exp Ther. 1963 Apr;140:31–40. [PubMed] [Google Scholar]
- Kao C. Y. Tetrodotoxin, saxitoxin and their significance in the study of excitation phenomena. Pharmacol Rev. 1966 Jun;18(2):997–1049. [PubMed] [Google Scholar]
- 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]
- 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]
- NARAHASHI T., YAMASAKI T. Mechanism of increase in negative after-potential by dicophanum (DDT) in the giant axons of the cockroach. J Physiol. 1960 Jun;152:122–140. doi: 10.1113/jphysiol.1960.sp006475. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Narahashi T., Haas H. G. DDT: interaction with nerve membrane conductance changes. Science. 1967 Sep 22;157(3795):1438–1440. doi: 10.1126/science.157.3795.1438. [DOI] [PubMed] [Google Scholar]
- Narahashi T., Haas H. G., Therrien E. F. Saxitoxin and tetrodotoxin: comparison of nerve blocking mechanism. Science. 1967 Sep 22;157(3795):1441–1442. doi: 10.1126/science.157.3795.1441. [DOI] [PubMed] [Google Scholar]
- SCHANTZ E. J. Biochemical studies on paralytic shellfish poisons. Ann N Y Acad Sci. 1960 Nov 17;90:843–855. doi: 10.1111/j.1749-6632.1960.tb26427.x. [DOI] [PubMed] [Google Scholar]
- 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]