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. 1979 Dec;297:423–442. doi: 10.1113/jphysiol.1979.sp013049

Differential effect of perhydrohistrionicotoxin on 'intrinsic' and 'extrinsic' end-plate responses.

E X Albuquerque, P W Gage, A C Oliveira
PMCID: PMC1458729  PMID: 317106

Abstract

1. At rat and frog neuromuscular junctions, perhydrohistrionicotoxin (H12-HTX), at concentrations below 10(-6) M, blocked end-plate currents and potentials generated by ionophoretic application of ACh (extrinsic responses) more effectively than end-plate currents and potentials generated by neurotransmitter secreted from the motor nerve (intrinsic responses). 2. In contrast, (+)-tubocurarine affected both extrinsic and intrinsic responses in a parallel manner. 3. There was no change in the time course and little or no change in the amplitude of intrinsic end-plate currents when extrinsic currents were depressed by H12-HTX nor was there any change in the conductance or lifetime of channels activated by applied ACh. 4. The depressant effect of H12-HTX on extrinsic responses persisted both when carbachol was used as the agonist and when acetylcholinesterase was inhibited with diisopropylfluorophosphate. 5. Large end-plate currents elicited by nerve stimulation that presumably activate the whole end-plate area were not depressed by H12-HTX to the same degree as extrinsic end-plate currents generated by ionophoresis of ACh at the same end-plate. 6. Brief (50 microsec) pulses of ACh produced brief end-plate potentials which were depressed by concentrations of H12-HTX that had little or no effect on miniature end-plate potentials. 7. Extrinsic responses to ACh at extrajunctional regions of denervated fibres were also depressed by low concentrations of H12-HTX. 8. It was concluded that the differential effects of H12-HTX on intrinsic and extrinsic end-plate responses could be due to the existence of two populations of receptor-channel complexes or to protection of local receptor-channel complexes from the toxin by a substance secreted from motor nerve terminals.

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Selected References

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  1. Adams P. R., Cash H. C., Quilliam J. P. Extrinsic and intrinsic acetylcholine and barbiturate effects on frog skeletal muscle. Br J Pharmacol. 1970 Nov;40(3):552P–553P. [PMC free article] [PubMed] [Google Scholar]
  2. Adams P. R. Drug blockade of open end-plate channels. J Physiol. 1976 Sep;260(3):531–552. doi: 10.1113/jphysiol.1976.sp011530. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Albuquerque E. X., Barnard E. A., Chiu T. H., Lapa A. J., Dolly J. O., Jansson S. E., Daly J., Witkop B. Acetylcholine receptor and ion conductance modulator sites at the murine neuromuscular junction: evidence from specific toxin reactions. Proc Natl Acad Sci U S A. 1973 Mar;70(3):949–953. doi: 10.1073/pnas.70.3.949. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Albuquerque E. X., Barnard E. A., Porter C. W., Warnick J. E. The density of acetylcholine receptors and their sensitivity in the postsynaptic membrane of muscle endplates. Proc Natl Acad Sci U S A. 1974 Jul;71(7):2818–2822. doi: 10.1073/pnas.71.7.2818. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Albuquerque E. X., Gage P. W. Differential effects of perhydrohistrionicotoxin on neurally and iontophoretically evoked endplate currents. Proc Natl Acad Sci U S A. 1978 Mar;75(3):1596–1599. doi: 10.1073/pnas.75.3.1596. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Albuquerque E. X., Kuba K., Daly J. Effect of histrionicotoxin on the ionic conductance modulator of the cholinergic receptor: a quantitative analysis of the end-plate current. J Pharmacol Exp Ther. 1974 May;189(2):513–524. [PubMed] [Google Scholar]
  7. Albuquerque E. X., McIsaac R. J. Early development of acetylcholine receptors on fast and slow mammalian skeletal muscle. Life Sci. 1969 Apr 1;8(7):409–416. doi: 10.1016/0024-3205(69)90235-5. [DOI] [PubMed] [Google Scholar]
  8. Anderson C. R., Stevens C. F. Voltage clamp analysis of acetylcholine produced end-plate current fluctuations at frog neuromuscular junction. J Physiol. 1973 Dec;235(3):655–691. doi: 10.1113/jphysiol.1973.sp010410. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Colquhoun D., Large W. A., Rang H. P. An analysis of the action of a false transmitter at the neuromuscular junction. J Physiol. 1977 Apr;266(2):361–395. doi: 10.1113/jphysiol.1977.sp011772. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. DEL CASTILLO J., KATZ B. The identity of intrinsic and extrinsic acetylcholine receptors in the motor end-plate. Proc R Soc Lond B Biol Sci. 1957 May 7;146(924):357–361. doi: 10.1098/rspb.1957.0016. [DOI] [PubMed] [Google Scholar]
  11. Daly J. W., Karle I., Myers C. W., Tokuyama T., Waters J. A., Witkop B. Histrionicotoxins: roentgen-ray analysis of the novel allenic and acetylenie spiroalkaloids isolated from a Colombian frog, Dendrobates histrionicus. Proc Natl Acad Sci U S A. 1971 Aug;68(8):1870–1875. doi: 10.1073/pnas.68.8.1870. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Dionne V. E., Stevens C. F. Voltage dependence of agonist effectiveness at the frog neuromuscular junction: resolution of a paradox. J Physiol. 1975 Oct;251(2):245–270. doi: 10.1113/jphysiol.1975.sp011090. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Dolly J. O., Albuquerque E. X., Sarvey J., Mallick B., Barnard E. A. Binding of perhydro-histrionicotoxin to the postsynaptic membrane of skeletal muscle in relation to its blockage of acetylcholine-induced depolarization. Mol Pharmacol. 1977 Jan;13(1):1–14. [PubMed] [Google Scholar]
  14. Eldefrawi A. T., Eldefrawi M. E., Albuquerque E. X., Oliveira A. C., Mansour N., Adler M., Daly J. W., Brown G. B., Burgermeister W., Witkop B. Perhydrohistrionicotoxin: a potential ligand for the ion conductance modulator of the acetylcholine receptor. Proc Natl Acad Sci U S A. 1977 May;74(5):2172–2176. doi: 10.1073/pnas.74.5.2172. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Ellisman M. H., Rash J. E., Staehelin L. A., Porter K. R. Studies of excitable membranes. II. A comparison of specializations at neuromuscular junctions and nonjunctional sarcolemmas of mammalian fast and slow twitch muscle fibers. J Cell Biol. 1976 Mar;68(3):752–774. doi: 10.1083/jcb.68.3.752. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Gage P. W., Eisenberg R. S. Action potentials, afterpotentials, and excitation-contraction coupling in frog sartorius fibers without transverse tubules. J Gen Physiol. 1969 Mar;53(3):298–310. doi: 10.1085/jgp.53.3.298. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Gage P. W., McBurney R. N., Van Helden D. Octanol reduces end-plate channel lifetime. J Physiol. 1978 Jan;274:279–298. doi: 10.1113/jphysiol.1978.sp012147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Gage P. W., Van Helden D. Effects of permeant monovalent cations on end-plate channels. J Physiol. 1979 Mar;288:509–528. [PMC free article] [PubMed] [Google Scholar]
  19. Glavinović M., Henry J. L., Kato G., Krnjević K., Puil E. Histrionicotoxin: effects on some central and peripheral excitable cells. Can J Physiol Pharmacol. 1974 Dec;52(6):1220–1226. doi: 10.1139/y74-161. [DOI] [PubMed] [Google Scholar]
  20. Kato G., Changeux J. P. Studies on the effect of histrionicotoxin on the monocellular electroplax from Electrophorus electricus and on the binding of (3H)acetylcholine to membrane fragments from Torpedo marmorata. Mol Pharmacol. 1976 Jan;12(1):92–100. [PubMed] [Google Scholar]
  21. Katz B., Miledi R. The binding of acetylcholine to receptors and its removal from the synaptic cleft. J Physiol. 1973 Jun;231(3):549–574. doi: 10.1113/jphysiol.1973.sp010248. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Katz B., Miledi R. The reversal potential at the desensitized endplate. Proc R Soc Lond B Biol Sci. 1977 Nov 14;199(1135):329–334. doi: 10.1098/rspb.1977.0144. [DOI] [PubMed] [Google Scholar]
  23. Katz B., Miledi R. The statistical nature of the acetycholine potential and its molecular components. J Physiol. 1972 Aug;224(3):665–699. doi: 10.1113/jphysiol.1972.sp009918. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Lapa A. J., Albuquerque E. X., Sarvey J. M., Daly J., Witkop B. Effects of histrionicotoxin on the chemosensitive and electrical properties of skeletal muscle. Exp Neurol. 1975 Jun;47(3):558–580. doi: 10.1016/0014-4886(75)90088-6. [DOI] [PubMed] [Google Scholar]
  25. Magleby K. L., Stevens C. F. A quantitative description of end-plate currents. J Physiol. 1972 May;223(1):173–197. doi: 10.1113/jphysiol.1972.sp009840. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Musick J., Hubbard J. I. Release of protein from mouse motor nerve terminals. Nature. 1972 Jun 2;237(5353):279–281. doi: 10.1038/237279a0. [DOI] [PubMed] [Google Scholar]
  27. Sobel A., Heidmann T., Hofler J., Changeux J. P. Distinct protein components from Torpedo marmorata membranes carry the acetylcholine receptor site and the binding site for local anesthetics and histrionicotoxin. Proc Natl Acad Sci U S A. 1978 Jan;75(1):510–514. doi: 10.1073/pnas.75.1.510. [DOI] [PMC free article] [PubMed] [Google Scholar]

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