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. 1992 Jan;105(1):113–118. doi: 10.1111/j.1476-5381.1992.tb14220.x

The effects of vesamicol on trains of endplate currents and on focally recorded nerve terminal currents at mammalian neuromuscular junctions.

K E Pemberton 1, C Prior 1, I G Marshall 1
PMCID: PMC1908631  PMID: 1375854

Abstract

1. The effects of vesamicol, an inhibitor of vesicular acetylcholine (ACh) storage, were studied on trains of endplate currents (e.p.cs) in the cut rat hemidiaphragm nerve-muscle preparation and on trains of focally recorded nerve terminal current waveforms in the mouse triangularis sterni nerve-muscle preparation. 2. In the rat, 0.1 and 1 microM (-)-vesamicol produced an enhancement of the rundown of e.p.c. amplitudes during trains of high frequency (50 Hz) nerve stimulation. However, 1 microM (+)-vesamicol had no effect on the rundown of e.p.c. amplitudes. 3. In the mouse, high concentrations of (-)-vesamicol (10-100 microM) produced a concentration- and stimulation-dependent decrease in the amplitude of the second negative-going deflection of focally recorded nerve terminal current waveforms. 4. At 1 mM, (-)-vesamicol produced a stimulation-independent decrease in the amplitude of the first negative-going deflection of the nerve terminal current waveforms, an increase in signal delay and evidence of nerve conduction failure. These all indicate a local anaesthetic-like block of nodal Na(+)-channels. 5. In contrast to its effects on trains of e.p.cs, the effects of vesamicol on the nerve terminal current waveforms were not stereoselective, the (+)-isomer being equipotent with the (-)-isomer. 6. Low concentrations of the Na(+)-channel blocking toxin, tetrodotoxin (15-60 nM), produced similar changes in the focally recorded nerve terminal current waveforms to those seen with vesamicol. 7. It is concluded that the stereoselective rundown of e.p.c. amplitudes produced by (-)-vesamicol is due to an effect, either direct or indirect, on ACh mobilization within motor nerve terminals.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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  1. Anderson D. C., King S. C., Parsons S. M. Pharmacological characterization of the acetylcholine transport system in purified Torpedo electric organ synaptic vesicles. Mol Pharmacol. 1983 Jul;24(1):48–54. [PubMed] [Google Scholar]
  2. Bahr B. A., Parsons S. M. Demonstration of a receptor in Torpedo synaptic vesicles for the acetylcholine storage blocker L-trans-2-(4-phenyl[3,4-3H]-piperidino) cyclohexanol. Proc Natl Acad Sci U S A. 1986 Apr;83(7):2267–2270. doi: 10.1073/pnas.83.7.2267. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Barstad J. A., Lilleheil G. Transversaly cut diaphragm preparation from rat. An adjuvant tool in the study of the physiology and pbarmacology of the myoneural junction. Arch Int Pharmacodyn Ther. 1968 Oct;175(2):373–390. [PubMed] [Google Scholar]
  4. Bowman W. C., Prior C., Marshall I. G. Presynaptic receptors in the neuromuscular junction. Ann N Y Acad Sci. 1990;604:69–81. doi: 10.1111/j.1749-6632.1990.tb31983.x. [DOI] [PubMed] [Google Scholar]
  5. Braga M. F., Harvey A. L., Rowan E. G. Effects of tacrine, velnacrine (HP029), suronacrine (HP128), and 3,4-diaminopyridine on skeletal neuromuscular transmission in vitro. Br J Pharmacol. 1991 Apr;102(4):909–915. doi: 10.1111/j.1476-5381.1991.tb12275.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Enomoto K. Post- and presynaptic effects of vesamicol (AH5183) on the frog neuromuscular junction. Eur J Pharmacol. 1988 Mar 1;147(2):209–215. doi: 10.1016/0014-2999(88)90779-0. [DOI] [PubMed] [Google Scholar]
  7. Estrella D., Green K. L., Prior C., Dempster J., Halliwell R. F., Jacobs R. S., Parsons S. M., Parsons R. L., Marshall I. G. A further study of the neuromuscular effects of vesamicol (AH5183) and of its enantiomer specificity. Br J Pharmacol. 1988 Apr;93(4):759–768. doi: 10.1111/j.1476-5381.1988.tb11460.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gibb A. J., Marshall I. G. Pre-and post-junctional effects of tubocurarine and other nicotinic antagonists during repetitive stimulation in the rat. J Physiol. 1984 Jun;351:275–297. doi: 10.1113/jphysiol.1984.sp015245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Girod R., Loctin F., Dunant Y. Local anaesthetic activity of vesamicol in the electric organ of Torpedo. Eur J Pharmacol. 1991 Mar 19;195(1):1–9. doi: 10.1016/0014-2999(91)90375-z. [DOI] [PubMed] [Google Scholar]
  10. Glavinović M. I. Voltage clamping of unparalysed cut rat diaphragm for study of transmitter release. J Physiol. 1979 May;290(2):467–480. doi: 10.1113/jphysiol.1979.sp012784. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Konishi T., Sears T. A. Electrical activity of mouse motor nerve terminals. Proc R Soc Lond B Biol Sci. 1984 Jul 23;222(1226):115–120. doi: 10.1098/rspb.1984.0052. [DOI] [PubMed] [Google Scholar]
  12. Lundh H. Effects of 4-aminopyridine on neuromuscular transmission. Brain Res. 1978 Sep 22;153(2):307–318. doi: 10.1016/0006-8993(78)90409-2. [DOI] [PubMed] [Google Scholar]
  13. Mallart A. Electric current flow inside perineurial sheaths of mouse motor nerves. J Physiol. 1985 Nov;368:565–575. doi: 10.1113/jphysiol.1985.sp015876. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Marshall I. G. Studies on the blocking action of 2-(4-phenyl piperidino) cyclohexanol (AH5183). Br J Pharmacol. 1970 May;38(3):503–516. doi: 10.1111/j.1476-5381.1970.tb10592.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. McArdle J. J., Angaut-Petit D., Mallart A., Bournaud R., Faille L., Brigant J. L. Advantages of the triangularis sterni muscle of the mouse for investigations of synaptic phenomena. J Neurosci Methods. 1981 Aug;4(2):109–115. doi: 10.1016/0165-0270(81)90044-3. [DOI] [PubMed] [Google Scholar]
  16. Molgó J., Lemeignan M., Lechat P. Analysis of the action of 4-aminopyridine during repetitive stimulation at the neuromuscular junction. Eur J Pharmacol. 1979 Jan 15;53(3):307–311. doi: 10.1016/0014-2999(79)90138-9. [DOI] [PubMed] [Google Scholar]
  17. Prior C., Searl T., Marshall I. G. The effects of l-vesamicol on transmitter release from rat motor nerve terminals at high frequencies of nerve stimulation. Br J Pharmacol. 1989 Dec;98 (Suppl):826P–826P. [PubMed] [Google Scholar]
  18. Searl T., Prior C., Marshall I. G. The effects of L-vesamicol, an inhibitor of vesicular acetylcholine uptake, on two populations of miniature endplate currents at the snake neuromuscular junction. Neuroscience. 1990;35(1):145–156. doi: 10.1016/0306-4522(90)90129-r. [DOI] [PubMed] [Google Scholar]
  19. Van der Kloot W. 2-(4-phenylpiperidino) cyclohexanol (AH5183) decreases quantal size at the frog neuromuscular junction. Pflugers Arch. 1986 Jan;406(1):83–85. doi: 10.1007/BF00582958. [DOI] [PubMed] [Google Scholar]
  20. Wannan G., Prior C., Marshall I. G. Alpha-adrenoceptor blocking properties of vesamicol. Eur J Pharmacol. 1991 Aug 16;201(1):29–34. doi: 10.1016/0014-2999(91)90318-k. [DOI] [PubMed] [Google Scholar]

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