Abstract
Biochemical progress toward the mechanism of voltage-dependent Na+ channels has enjoyed the benefit of an extensive molecular pharmacology that includes natural specific toxins as well as synthetic chemical probes of this channel. The recently introduced method of studying chemically activated Na+ channels in planar lipid bilayers with the use of batrachotoxin (Krueger et al., 1983) makes it possible to examine functional manifestations of Na+-channel pharmacology at the level of individual channel macromolecules. In this chapter, we summarize the results of our investigations of the blocking of batrachotoxin-activated Na+ channels from rat skeletal muscle by three classes of pharmacological agents: specific guanidinium toxins, synthetic organic cations, and local anesthetics.
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References
Albuquerque, E. X., Brookes, N., Onur, R., and Warnick, J. E., 1976, Kinetics of interaction of batrachotoxin and tetrodotoxin on rat diaphram muscle, Mol. Pharmacol. 12:82–91.
Armstrong, C. M., 1975, Potassium pores of nerve and muscle membranes, in: Membranes: A Series of Advances (G. Eisenman, ed.), pp. 325-358, Marcel Dekker, New York.
Bell, J. E., and Miller, C., 1984, Effects of phospholipid surface charge on ion conduction in the K+ channel of sarcoplasmic reticulum, Biophys. J. 45:279–287.
Cahalan, M. D., and Almers, W., 1979, Interactions between quaternary lidocaine, the sodium channel gates, and tetrodotoxin, Biophys. J. 27:39–56.
Creveling, C. R., McNeal, E. T., Daley, J. W., and Brown, G. B., 1983, Batrachotoxin-induced depolarization and [3H]bactrachotoxinin-A 20 α-benzoate binding in a vesicular preparation from guinea pig cerebral cortex: Inhibition by local anesthetics, Mol. Pharmacol. 23:350–358.
Cruz, L. J., Gray, W. R., Olivera, B. M., Zeikus, R. D., Kerr, L., Yoshikami, D., and Moczydlowski, E., 1985, Conus geographus toxins that discriminate between neuronal and muscle sodium channels, J. Biol. Chem. 260:9280–9288.
French, R. J., Worley, J. F., and Krueger, B. K., 1984, Voltage-dependent block by saxitoxin of sodium channels incorporated in planar lipid bilayers, Biophys. J. 45:301–312.
Hall, S., 1982, Toxins and Toxicity of Protogonyaulax from the Northeast Pacific, Ph.D. Thesis. University of Alaska, Fairbanks.
Hall, S., Reichardt, P. B., and Neve, R. A., 1980, Toxins extracted from an Alaskan isolate of Protogonyaulax sp, Biochem. Biophys. Res. Commun. 97:649–653.
Hartshorne, R. P., Keller, B. U., Talvenheimo, J. A., Catterall, W. A., and Montai, M., 1985, Functional reconstitution of the purified brain sodium channel in planar lipid bilayers, Proc. Natl. Acad. Sci. U.S.A. 82:240–244.
Henderson, R., Ritchie, J. M., and Strichartz, G. R., 1974, Evidence that tetrodotoxin and saxitoxin act at a metal cation binding site in the sodium channel of nerve membrane, Proc. Natl. Acad. Sci. U.S.A. 71:3936–3940.
Hille, B., 1975, The receptor for tetrodotoxin and saxitoxin: A structural hypothesis, Biophys. J. 15:615–619.
Hille, B., 1977a, The pH-dependent rate of action of local anesthetics on the node of Ranvier, J. Gen. Physiol. 69:475–496.
Hille, B., 1977b, Local anesthetics: Hydrophilic and hydrophobic pathways for the drug-receptor reaction, J. Gen. Physiol. 69:497–515.
Hille, B., Ritchie, J. R., and Strichartz, G. R., 1975, The effect of surface charge on the nerve membrane in the action of tetrodotoxin and saxitoxin in frog myelinated nerve, J. Physiol. (Lond.) 250:34-35P.
Horn, R., Patlak, J., and Stevens, C. F., 1981, The effect of tetramethylammonium on single sodium channel currents, Biophys. J. 36:321–327.
Huang, L. M., and Ehrenstein, G., 1981, Local anesthetics QX-572 and benzocaine act at separate sites on the batrachotoxin-activated sodium channel, J. Gen. Physiol. 77:137–153.
Jencks, W. P., 1981, On the attribution and additivity of binding energies, Proc. Natl. Acad. Sci. U.S.A. 78:4046–4050.
Kao, C. Y., and Nishiyama, A., 1965, Action of saxitoxin on peripheral neuromuscular systems, J. Physiol. (Lond.) 180:50-66.
Kao, C. Y., and Walker, S. E., 1982, Active groups of saxitoxin and tetrodotoxin as deduced from actions of saxitoxin analogues on frog muscle and squid axon, J. Physiol. (Lond.) 323:619-637.
Khodorov, B. L., Peganov, E. M., Revenko, S. V., and Shishkova, L. D., 1975, Sodium currents in voltage clamped nerve fiber of frog under the combined action of batrachotoxin and procaine, Brain Res. 84:541–546.
Krueger, B. K., Worley, J. F., and French, R. J., 1983, Single sodium channels from rat brain incorporated into planar lipid bilayer membranes, Nature 303:172–175.
McLaughlin, S., 1977, Electrostatic potentials at membrane-solution interfaces, Curr. Top. Membr. Transport 9:71–144.
Miller, J. A., Agnew, W. S., and Levinson, S. R., 1983, Principal glycopeptide of the tetrodotoxin/ saxitoxin binding protein from Electrophorus electricus: Isolation and partial chemical and physical characterization, Biochemistry 22:462–470.
Moczydlowski, E., Garber, S. S., and Miller, C., 1984a, Batrachotoxin-activated Na+ channels in planar lipid bilayers: Competition of tetrodotoxin block by Na+, J. Gen. Physiol. 84:665–686.
Moczydlowski, E., Hall, S., Garber, S. S., Strichartz, G. S., and Miller, C., 1984b, Voltage-dependent blockade of muscle Na+ channels by guanidinium toxins: Effect of toxin charge, J. Gen. Physiol. 84:687–704.
Postma, S. W., and Catterall, W. A., 1984, Inhibition of binding of [3H]batrachotoxin in A 20-α-benzoate to sodium channels by local anesthetics, Mol. Pharmacol. 25:219–227.
Rogers, R. S., and Rapoport, H., 1980, The pKa’s of saxitoxin, J. Am. Chem. Soc. 102:7335–7339.
Sato, S., Nakamura, H., Ohizumi, Y., Kobayashi, J., and Hirata, Y., 1983, The amino acid sequences of homologous hydroxyproline-containing myotoxins from the marine snail Conus geographus venom, FEBS Lett. 155:277–280.
Shimizu, Y., Hsu, C., Fallon, W. E., Oshima, Y., Miura, I., and Nokanishi, K., 1978, Structure of neosaxitoxin, J. Am. Chem. Soc. 100:6791–6793.
Shimizu, Y., Hsu, C., and Genenah, A., 1981, Structure of saxitoxin in solution and stereochemistry of dihydrosaxitoxins, J. Am. Chem. Soc. 103:605–609.
Strichartz, G. R., 1973, The inhibition of sodium currents in myelinated nerve by quaternary derivatives of lidocaine, J. Gen. Physiol. 62:37–57.
Strichartz, G., 1976, Molecular mechanisms of nerve block by local anesthetics, Anesthesiology 45:421–441.
Strichartz, G., 1984, Structural determinants of the affinity of saxitoxin for neuronal sodium channels: Electrophysiological studies on frog peripheral nerve, J. Gen. Physiol. 84:281–305.
Strichartz, G. R., and Ritchie, J. M., 1985, The action of local anesthetics on ion channels of excitable tissues, in: Handbook of Experimental Pharmacology: Local Anesthetics (G. Strichartz, ed.), Springer, New York (in press).
Woodhull, A., 1973, Ionic blockage of sodium channels in nerve, J. Gen. Physiol. 61:687–708.
Yamamoto, D., and Yeh, J. Z., 1984, Kinetics of 9-aminoacridine block of single Na channels, J. Gen. Physiol. 84:361–377.
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© 1986 Springer Science+Business Media New York
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Moczydlowski, E., Uehara, A., Hall, S. (1986). Blocking Pharmacology of Batrachotoxin-Activated Sodium Channels. In: Miller, C. (eds) Ion Channel Reconstitution. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-1361-9_16
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DOI: https://doi.org/10.1007/978-1-4757-1361-9_16
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