Abstract
The voltage dependence of the voltage clamp responses of myelinated nerve fibers depends on the concentration of divalent cations and of hydrogen ions in the bathing medium. In general, increases of the [Ca], [Ni], or [H] increase the depolarization needed to elicit a given response of the nerve. An e-fold increase of the [Ca] produces the following shifts of the voltage dependence of the parameters in the Hodgkin-Huxley model: m ∞, 8.7 mv; h ∞, 6.5 mv; τn, 0.0 mv. The same increase of the [H], if done below pH 5.5, produces the following shifts: m ∞, 13.5 mv; h ∞, 13.5 mv; τn, 13.5 mv; and if done above pH 5.5: m ∞, 1.3 mv; h ∞, 1.3 mv; τn, 4.0 mv. The voltage shifts are proportional to the logarithm of the concentration of the divalent ions and of the hydrogen ion. The observed voltage shifts are interpreted as evidence for negative fixed charges near the sodium and potassium channels. The charged groups are assumed to comprise several types, of varying affinity for divalent and hydrogen ions. The charges near the sodium channels differ from those near the potassium channels. As the pH is lowered below pH 6, the maximum sodium conductance decreases quickly and reversibly in a manner that suggests that the protonation of an acidic group with a pKa of 5.2 blocks individual sodium channels.
Full Text
The Full Text of this article is available as a PDF (975.2 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- 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]
 - CARVALHO A. P., SANUI H., PACE N. CALCIUM AND MAGNESIUM BINDING PROPERTIES OF CELL MEMBRANE MATERIALS. J Cell Physiol. 1963 Dec;62:311–317. doi: 10.1002/jcp.1030620311. [DOI] [PubMed] [Google Scholar]
 - 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]
 - Chandler W. K., Hodgkin A. L., Meves H. The effect of changing the internal solution on sodium inactivation and related phenomena in giant axons. J Physiol. 1965 Oct;180(4):821–836. doi: 10.1113/jphysiol.1965.sp007733. [DOI] [PMC free article] [PubMed] [Google Scholar]
 - 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]
 - DODGE J. T., MITCHELL C., HANAHAN D. J. The preparation and chemical characteristics of hemoglobin-free ghosts of human erythrocytes. Arch Biochem Biophys. 1963 Jan;100:119–130. doi: 10.1016/0003-9861(63)90042-0. [DOI] [PubMed] [Google Scholar]
 - Elul R. Fixed charge in the cell membrane. J Physiol. 1967 Apr;189(3):351–365. doi: 10.1113/jphysiol.1967.sp008173. [DOI] [PMC free article] [PubMed] [Google Scholar]
 - GENT W. L., TROUNCE J. R., WALSER M. THE BINDING OF CALCIUM ION BY THE HUMAN ERYTHROCYTE MEMBRANE. Arch Biochem Biophys. 1964 Jun;105:582–589. doi: 10.1016/0003-9861(64)90054-2. [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]
 - Hille B. Pharmacological modifications of the sodium channels of frog nerve. J Gen Physiol. 1968 Feb;51(2):199–219. doi: 10.1085/jgp.51.2.199. [DOI] [PMC free article] [PubMed] [Google Scholar]
 - 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]
 - Hutter O. F., Warner A. E. The pH sensitivity of the chloride conductance of frog skeletal muscle. J Physiol. 1967 Apr;189(3):403–425. doi: 10.1113/jphysiol.1967.sp008176. [DOI] [PMC free article] [PubMed] [Google Scholar]
 - JULIAN F. J., MOORE J. W., GOLDMAN D. E. Current-voltage relations in the lobster giant axon membrane under voltage clamp conditions. J Gen Physiol. 1962 Jul;45:1217–1238. doi: 10.1085/jgp.45.6.1217. [DOI] [PMC free article] [PubMed] [Google Scholar]
 - 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]
 - SEAMAN G. V., UHLENBRUCK G. The surface structure of erythrocytes from some animal sources. Arch Biochem Biophys. 1963 Mar;100:493–502. doi: 10.1016/0003-9861(63)90117-6. [DOI] [PubMed] [Google Scholar]
 - SHANES A. M. Electrochemical aspects of physiological and pharmacological action in excitable cells. II. The action potential and excitation. Pharmacol Rev. 1958 Jun;10(2):165–273. [PubMed] [Google Scholar]
 
