Blocking Pharmacology of Batrachotoxin-Activated Sodium Channels
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.
KeywordsLocal Anesthetic Sodium Channel Voltage Dependence Organic Cation Dissociation Rate Constant
Unable to display preview. Download preview PDF.
- 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.Google Scholar
- Hall, S., 1982, Toxins and Toxicity of Protogonyaulax from the Northeast Pacific, Ph.D. Thesis. University of Alaska, Fairbanks.Google Scholar
- 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.Google Scholar
- Kao, C. Y., and Nishiyama, A., 1965, Action of saxitoxin on peripheral neuromuscular systems, J. Physiol. (Lond.) 180:50-66.Google Scholar
- 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.Google Scholar
- 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).Google Scholar