Reversal by cysteine of the cadmium-induced block of skeletal neuromuscular transmission in vitro

M.F.M. Braga, E.G. Rowan

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Abstract

1. Neuromuscular transmission in isolated nerve-muscle preparations was blocked by exposure to Cd2+ for less than 30 min or more than 2 h. The abilities of cysteine, Ca2+ or 3,4-diaminopyridine (3,4-DAP) to reverse the blockade induced by Cd2+ were studied. 2. On the mouse hemidiaphragm preparation, exposure to Cd2+ (10 microM) for 10 to 20 min induced a blockade which was easily reversed by increasing the extracellular Ca2+ concentration (5-10 mM) or by 3,4-DAP (100 microM). Exposure to Cd2+ (3-10 microM) for over 2 h led to a blockade which was not reversed by Ca2+ (5-15 mM) or 3,4-DAP (100 microM). Cysteine (1 mM) was able to reverse completely the blockade induced by both brief and prolonged exposures to Cd2+. 3. In chick biventer cervicis preparations, Cd2+ (100 microM) decreased the twitch height of indirectly stimulated preparations without affecting responses to exogenously applied acetylcholine, carbachol or KCl. Cysteine (1-3 mM) had no appreciable effect on twitch responses to indirect stimulation or to exogenously applied agonists but fully reversed the blockade induced by Cd2+ (100 microM). 4. In mouse triangularis sterni preparations, Cd2+ (1-30 microM) depressed the evoked quantal release of acetylcholine. Concentrations of Cd2+ which completely blocked endplate potentials (e.p.ps) were without significant effect on miniature endplate potential (m.e.p.p.) amplitude and frequency or time constant of decay. Cysteine (1-10 mM) alone had no effect on e.p.ps or m.e.p.ps, but completely reversed the blockade induced by Cd2+.6. In addition to the competitive blocking action of Cd2+ at the prejunctional Ca2+ channels, long exposure to Cd2+ leads to a blockade that is not competitive. This probably involves binding of Cd2+" at an extracellular thiol site on, or close to, voltage-operated Ca2+' channels.
Original languageEnglish
Pages (from-to)95-100
Number of pages5
JournalBritish Journal of Pharmacology
Volume107
Issue number1
Publication statusPublished - Sep 1992

Keywords

  • motor nerve terminals
  • transmitter release
  • channels
  • nerve endings
  • diamide
  • muscle

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