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British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1992 Jan;105(1):23–26. doi: 10.1111/j.1476-5381.1992.tb14205.x

Indirect inhibitory effect of succinylcholine on acetylcholine-activated channel activities and its modulation by external Ca2+ in mouse skeletal muscles.

H Nojima 1, M Muroi 1, I Kimura 1, M Kimura 1
PMCID: PMC1908628  PMID: 1317736

Abstract

1. The effect of extracellular calcium on single acetylcholine (ACh)-activated channel activities when desensitizing concentrations of succinylcholine (SuCh) were applied to the surrounding endplate membrane was investigated by the cell-attached patch-clamp technique at endplates of single skeletal muscle (flexor digitorum brevis) fibres of adult mice. 2. Bath-applied SuCh (0.1-3 microM, in 2.5 mM Ca2+) increased in a concentration-dependent manner the mean open time of ACh-activated channel currents recorded at membrane potentials which cancelled the SuCh-induced depolarizations. 3. In the presence of 0.5 and 2.5 mM external Ca2+, SuCh (3 microM) applied outside the patch pipette prolonged the mean open time of ACh-activated channel currents in a time-dependent manner (by 45% and 52%, respectively), and simultaneously significantly decreased the single channel conductance (by 14% and 10%, respectively). These SuCh-induced effects did not occur in a nominally Ca(2+)-free extracellular medium. 4. Under the same conditions, SuCh (3 microM) augmented the time-dependent decline in the opening frequency of ACh-activated channel currents obtained in nominally Ca(2+)-free medium. 5. These results suggest that external calcium ions act to modulate nicotinic ACh receptor channel activity, and accelerate desensitization of the receptor.

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Selected References

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  1. 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]
  2. Anwyl R., Narahashi T. Comparison of desensitization and time-dependent block of the acetylcholine receptor responses by chlorpromazine, cytochalasin B, triton X-100 and other agents. Br J Pharmacol. 1980 May;69(1):99–106. doi: 10.1111/j.1476-5381.1980.tb10887.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Aracava Y., Ikeda S. R., Daly J. W., Brookes N., Albuquerque E. X. Interactions of bupivacaine with ionic channels of the nicotinic receptor. Analysis of single-channel currents. Mol Pharmacol. 1984 Sep;26(2):304–313. [PubMed] [Google Scholar]
  4. Burgermeister W., Catterall W. A., Witkop B. Histrionicotoxin enhances agonist-induced desensitization of acetylcholine receptor. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5754–5758. doi: 10.1073/pnas.74.12.5754. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chesnut T. J. Two-component desensitization at the neuromuscular junction of the frog. J Physiol. 1983 Mar;336:229–241. doi: 10.1113/jphysiol.1983.sp014578. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Colquhoun D., Ogden D. C. Activation of ion channels in the frog end-plate by high concentrations of acetylcholine. J Physiol. 1988 Jan;395:131–159. doi: 10.1113/jphysiol.1988.sp016912. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dionne V. E. Two types of nicotinic acetylcholine receptor channels at slow fibre end-plates of the garter snake. J Physiol. 1989 Feb;409:313–331. doi: 10.1113/jphysiol.1989.sp017499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Durant N. N., Katz R. L. Suxamethonium. Br J Anaesth. 1982 Feb;54(2):195–208. doi: 10.1093/bja/54.2.195. [DOI] [PubMed] [Google Scholar]
  9. Eusebi F., Grassi F., Molinaro M., Zani B. M. Acetylcholine regulation of nicotinic receptor channels through a putative G protein in chick myotubes. J Physiol. 1987 Dec;393:635–645. doi: 10.1113/jphysiol.1987.sp016845. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fiekers J. F., Spannbauer P. M., Scubon-Mulieri B., Parsons R. L. Voltage dependence of desensitization. Influence of calcium and activation kinetics. J Gen Physiol. 1980 May;75(5):511–529. doi: 10.1085/jgp.75.5.511. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Greenberg A. S., Nakajima S., Nakajima Y. Functional properties of newly inserted acetylcholine receptors in embryonic Xenopus muscle cells. Brain Res. 1985 Apr;351(2):289–296. doi: 10.1016/0165-3806(85)90200-7. [DOI] [PubMed] [Google Scholar]
  12. Hamill O. P., Marty A., Neher E., Sakmann B., Sigworth F. J. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch. 1981 Aug;391(2):85–100. doi: 10.1007/BF00656997. [DOI] [PubMed] [Google Scholar]
  13. Heidmann T., Oswald R. E., Changeux J. P. Multiple sites of action for noncompetitive blockers on acetylcholine receptor rich membrane fragments from torpedo marmorata. Biochemistry. 1983 Jun 21;22(13):3112–3127. doi: 10.1021/bi00282a014. [DOI] [PubMed] [Google Scholar]
  14. Hopfield J. F., Tank D. W., Greengard P., Huganir R. L. Functional modulation of the nicotinic acetylcholine receptor by tyrosine phosphorylation. Nature. 1988 Dec 15;336(6200):677–680. doi: 10.1038/336677a0. [DOI] [PubMed] [Google Scholar]
  15. KATZ B., THESLEFF S. A study of the desensitization produced by acetylcholine at the motor end-plate. J Physiol. 1957 Aug 29;138(1):63–80. doi: 10.1113/jphysiol.1957.sp005838. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kimura I., Kondoh T., Kimura M. Changes in intracellular Ca2+ produced in the mouse diaphragm by neuromuscular blocking drugs. J Pharm Pharmacol. 1990 Sep;42(9):626–631. doi: 10.1111/j.2042-7158.1990.tb06620.x. [DOI] [PubMed] [Google Scholar]
  17. Magazanik L. G., Nikolsky E., Vyskocil F. Effect of the desensitization-potentiating agent SKF-525a on frog end-plate currents. Eur J Pharmacol. 1982 May 7;80(1):115–119. doi: 10.1016/0014-2999(82)90185-6. [DOI] [PubMed] [Google Scholar]
  18. Magazanik L. G., Vyskocil F. Dependence of acetylcholine desensitization on the membrane potential of frog muscle fibre and on the ionic changes in the medium. J Physiol. 1970 Oct;210(3):507–518. doi: 10.1113/jphysiol.1970.sp009223. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Miledi R. Intracellular calcium and desensitization of acetylcholine receptors. Proc R Soc Lond B Biol Sci. 1980 Sep 26;209(1176):447–452. doi: 10.1098/rspb.1980.0106. [DOI] [PubMed] [Google Scholar]
  20. Miledi R., Parker I., Schalow G. Transmitter induced calcium entry across the post-synaptic membrane at frog end-plates measured using arsenazo III. J Physiol. 1980 Mar;300:197–212. doi: 10.1113/jphysiol.1980.sp013158. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Sakmann B., Patlak J., Neher E. Single acetylcholine-activated channels show burst-kinetics in presence of desensitizing concentrations of agonist. Nature. 1980 Jul 3;286(5768):71–73. doi: 10.1038/286071a0. [DOI] [PubMed] [Google Scholar]

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