title: Reversal by cysteine of the cadmium-induced block of skeletal neuromuscular transmission in vitro.
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.
authors.affiliation: Department of Physiology and Pharmacology, Strathcylde Institute for Drug Research, University of Strathclyde, Glasgow.
authors.forename: M F
authors.initials: MF
authors.lastname: Braga
authors.forename: E G
authors.initials: EG
authors.lastname: Rowan
mesh_terms: D015761:4-Aminopyridine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000109:Acetylcholine / Q000378:metabolism; D000077770:Amifampridine; D000818:Animals; D002104:Cadmium / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D003545:Cysteine / Q000494:pharmacology*; D003964:Diaphragm; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D009045:Motor Endplate / Q000187:drug effects / Q000502:physiology; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000502:physiology; D011188:Potassium / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects*
chemical_list: D002104:Cadmium; D000001:Calcimycin; D015761:4-Aminopyridine; D003545:Cysteine; D000109:Acetylcholine; D000077770:Amifampridine; D011188:Potassium; D002118:Calcium