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. 1990 Dec;101(4):793–798. doi: 10.1111/j.1476-5381.1990.tb14159.x

Facilitation by 3,4-diaminopyridine of regenerative acetylcholine release from mouse motor nerve.

S J Hong 1, C C Chang 1
PMCID: PMC1917818  PMID: 1964819

Abstract

1. Effects of 3,4-diaminopyridine (DAP) on endplate potentials (e.p.ps) were studied in mouse phrenic nerve-hemidiaphragms. 2. In cut muscle preparations, low concentrations of DAP (2-20 microns) increased the amplitude of e.p.ps and shifted the curve relating Ca2+ concentration to e.p.p. amplitude leftward. 3. High concentration of DAP (40-4000 microns) prolonged the duration of e.p.ps dose-dependently up to one hundred fold (ca. 200 ms), yielding, in addition to the normal phasic e.p.p., a prolonged plateau depolarization component which was often preceded by an upstroke depolarization. During the plateau depolarization, nerve stimulations did not evoke any e.p.p. 4. The plateau component of prolonged e.p.ps was suppressed by tubocurarine, verapamil, nifedipine, Mn2+ and Cd2+ (but not by atropine) at low concentrations that had negligible effect on the amplitude of miniature e.p.ps or the phasic component of e.p.ps. Abolition of the plateau component by these agents restored the capability of the nerve terminal to evoke e.p.ps on nerve stimulation. 5. Low concentrations of neostigmine (0.01-0.02 microns) markedly lengthened DAP-prolonged e.p.ps. However, the regenerative endplate depolarization evoked in the presence of high concentrations of neostigmine (0.3-0.5 microns) was not prolonged by DAP. 6. Tetraethylammonium (1 mM) did not provoke prolonged e.p.ps but acted cooperatively with DAP to prolong the duration of plateau depolarization. At a high concentration (3 mM), tetraethylammonium depressed the amplitude of miniature e.p.ps and abolished DAP-prolonged e.p.ps. 7. In uncut muscle preparations, DAP apparently did not modify the time course and amplitude of miniature e.p.ps.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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  1. Bostock H., Sears T. A., Sherratt R. M. The effects of 4-aminopyridine and tetraethylammonium ions on normal and demyelinated mammalian nerve fibres. J Physiol. 1981;313:301–315. doi: 10.1113/jphysiol.1981.sp013666. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bowman W. C., Harvey A. L., Marshall I. G. The actions of aminopyridines on avian muscle. Naunyn Schmiedebergs Arch Pharmacol. 1977 Mar;297(1):99–103. doi: 10.1007/BF00508816. [DOI] [PubMed] [Google Scholar]
  3. Brigant J. L., Mallart A. Presynaptic currents in mouse motor endings. J Physiol. 1982 Dec;333:619–636. doi: 10.1113/jphysiol.1982.sp014472. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chang C. C., Chen S. M., Hong S. J. Reversals of the neostigmine-induced tetanic fade and endplate potential run-down with respect to the autoregulation of transmitter release. Br J Pharmacol. 1988 Dec;95(4):1255–1261. doi: 10.1111/j.1476-5381.1988.tb11762.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chang C. C., Hong S. J. A regenerating release of acetylcholine from mouse motor nerve terminals treated with anticholinesterase agents. Neurosci Lett. 1986 Aug 29;69(2):203–207. doi: 10.1016/0304-3940(86)90604-x. [DOI] [PubMed] [Google Scholar]
  6. Chiarandini D. J., Stefani E. Calcium action potentials in rat fast-twitch and slow-twitch muscle fibres. J Physiol. 1983 Feb;335:29–40. doi: 10.1113/jphysiol.1983.sp014516. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cook N. S. The pharmacology of potassium channels and their therapeutic potential. Trends Pharmacol Sci. 1988 Jan;9(1):21–28. doi: 10.1016/0165-6147(88)90238-6. [DOI] [PubMed] [Google Scholar]
  8. Corthay J., Dunant Y., Loctin F. Acetylcholine changes underlying transmission of a single nerve impulse in the presence of 4-aminopyridine in Torpedo. J Physiol. 1982 Apr;325:461–479. doi: 10.1113/jphysiol.1982.sp014162. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Garcia-Segura L. M., Muller D., Dunant Y. Increase in the number of presynaptic large intramembrane particles during synaptic transmission at the Torpedo nerve-electroplaque junction. Neuroscience. 1986 Sep;19(1):63–79. doi: 10.1016/0306-4522(86)90006-0. [DOI] [PubMed] [Google Scholar]
  10. Harvey A. L., Marshall I. G. The actions of three diaminopyridines on the chick biventer cervicis muscle. Eur J Pharmacol. 1977 Aug 15;44(4):303–309. doi: 10.1016/0014-2999(77)90303-x. [DOI] [PubMed] [Google Scholar]
  11. Heuser J. E., Reese T. S., Dennis M. J., Jan Y., Jan L., Evans L. Synaptic vesicle exocytosis captured by quick freezing and correlated with quantal transmitter release. J Cell Biol. 1979 May;81(2):275–300. doi: 10.1083/jcb.81.2.275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hong S. J., Chang C. C. Antagonism by tubocurarine and verapamil of the regenerative acetylcholine release from mouse motor nerve. Eur J Pharmacol. 1989 Mar 14;162(1):11–17. doi: 10.1016/0014-2999(89)90598-0. [DOI] [PubMed] [Google Scholar]
  13. Horn A. S., Lambert J. J., Marshall I. G. A comparison of the facilitatory actions of 4-aminopyridine methiodide and 4-aminopyridine on neuromuscular transmission. Br J Pharmacol. 1979 Jan;65(1):53–62. doi: 10.1111/j.1476-5381.1979.tb17333.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Illes P., Thesleff S. 4-Aminopyridine and evoked transmitter release from motor nerve endings. Br J Pharmacol. 1978 Dec;64(4):623–629. doi: 10.1111/j.1476-5381.1978.tb17325.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Katz B., Miledi R. Estimates of quantal content during 'chemical potentiation' of transmitter release. Proc R Soc Lond B Biol Sci. 1979 Aug 31;205(1160):369–378. doi: 10.1098/rspb.1979.0070. [DOI] [PubMed] [Google Scholar]
  16. Lee K. S., Tsien R. W. Mechanism of calcium channel blockade by verapamil, D600, diltiazem and nitrendipine in single dialysed heart cells. Nature. 1983 Apr 28;302(5911):790–794. doi: 10.1038/302790a0. [DOI] [PubMed] [Google Scholar]
  17. Llinás R., Walton K., Bohr V. Synaptic transmission in squid giant synapse after potassium conductance blockage with external 3- and 4-aminopyridine. Biophys J. 1976 Jan;16(1):83–86. doi: 10.1016/S0006-3495(76)85664-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. 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]
  19. Lundh H. Effects of 4-aminopyridine on statistical parameters of transmitter release at the neuromuscular junction. Acta Pharmacol Toxicol (Copenh) 1979 May;44(5):343–346. doi: 10.1111/j.1600-0773.1979.tb02341.x. [DOI] [PubMed] [Google Scholar]
  20. Magleby K. L., Terrar D. A. Factors affecting the time course of decay of end-plate currents: a possible cooperative action of acetylcholine on receptors at the frog neuromuscular junction. J Physiol. 1975 Jan;244(2):467–495. doi: 10.1113/jphysiol.1975.sp010808. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Mallart A. A calcium-activated potassium current in motor nerve terminals of the mouse. J Physiol. 1985 Nov;368:577–591. doi: 10.1113/jphysiol.1985.sp015877. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Molgó J., Lundh H., Thesleff S. Potency of 3,4-diaminopyridine and 4-aminopyridine on mammalian neuromuscular transmission and the effect of pH changes. Eur J Pharmacol. 1980 Jan 11;61(1):25–34. doi: 10.1016/0014-2999(80)90378-7. [DOI] [PubMed] [Google Scholar]
  23. Muller D. Potentiation by 4-aminopyridine of quantal acetylcholine release at the Torpedo nerve-electroplaque junction. J Physiol. 1986 Oct;379:479–493. doi: 10.1113/jphysiol.1986.sp016265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Penner R., Dreyer F. Two different presynaptic calcium currents in mouse motor nerve terminals. Pflugers Arch. 1986 Feb;406(2):190–197. doi: 10.1007/BF00586682. [DOI] [PubMed] [Google Scholar]
  25. Perreault P., Avoli M. Effects of low concentrations of 4-aminopyridine on CA1 pyramidal cells of the hippocampus. J Neurophysiol. 1989 May;61(5):953–970. doi: 10.1152/jn.1989.61.5.953. [DOI] [PubMed] [Google Scholar]
  26. Riker W. K., Matsumoto M., Takashima K. Synaptic facilitation by 3-aminopyridine and its antagonism by verapamil and diltiazem. J Pharmacol Exp Ther. 1985 Nov;235(2):431–435. [PubMed] [Google Scholar]
  27. Rogawski M. A., Barker J. L. Effects of 4-aminopyridine on calcium action potentials and calcium current under voltage clamp in spinal neurons. Brain Res. 1983 Nov 28;280(1):180–185. doi: 10.1016/0006-8993(83)91190-3. [DOI] [PubMed] [Google Scholar]
  28. Rowan E. G., Harvey A. L. Potassium channel blocking actions of beta-bungarotoxin and related toxins on mouse and frog motor nerve terminals. Br J Pharmacol. 1988 Jul;94(3):839–847. doi: 10.1111/j.1476-5381.1988.tb11595.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Simmons M. A., Dun N. J. Actions of 4-aminopyridine on mammalian ganglion cells. Brain Res. 1984 Apr 23;298(1):149–153. doi: 10.1016/0006-8993(84)91159-4. [DOI] [PubMed] [Google Scholar]
  30. Thesleff S. Aminopyridines and synaptic transmission. Neuroscience. 1980;5(8):1413–1419. doi: 10.1016/0306-4522(80)90002-0. [DOI] [PubMed] [Google Scholar]
  31. Yeh J. Z., Oxford G. S., Wu C. H., Narahashi T. Interactions of aminopyridines with potassium channels of squid axon membranes. Biophys J. 1976 Jan;16(1):77–81. doi: 10.1016/S0006-3495(76)85663-9. [DOI] [PMC free article] [PubMed] [Google Scholar]

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