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

• Published in: British journal of pharmacology 1992-09, Vol.107 (1), p.95-100
• Main Authors: Braga, M.F.M., Rowan, E.G.
• Format: Article
• Language: English
• Subjects: 4-Aminopyridine - analogs & derivatives; 4-Aminopyridine - pharmacology; Acetylcholine - metabolism; acetylcholine release; Amifampridine; Animals; Biological and medical sciences; Cadmium; Cadmium - pharmacology; Calcimycin - pharmacology; Calcium - pharmacology; calcium channels; Chemical and industrial products toxicology. Toxic occupational diseases; cysteine; Cysteine - pharmacology; Diaphragm; Female; In Vitro Techniques; Male; Medical sciences; Membrane Potentials - drug effects; Metals and various inorganic compounds; Mice; Mice, Inbred BALB C; Motor Endplate - drug effects; Motor Endplate - physiology; Neuromuscular Junction - drug effects; Neuromuscular Junction - physiology; neuromuscular transmission; perineural waveform; Potassium - metabolism; Synaptic Transmission - drug effects; Toxicology
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1992.tb14468.x

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 μm) 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 μm). Exposure to Cd2+ (3–10 μm) for over 2 h led to a blockade which was not reversed by Ca2+ (5–15 mm) or 3,4‐DAP (100 μm). 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 μm) 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 μm). 4 In mouse triangularis sterni preparations, Cd2+ (1–30 μm) 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+. 5 Extracellular recording of perineural waveforms from triangularis sterni preparations revealed that Cd2+ was able to block the long‐lasting positive component that is sensitive to Ca2+ channel blockers and the delayed negative deflection that is related to the Ca2+‐activated K+ current (IK,Ca) seen in the presence of 3,4‐DAP. Cysteine by itself had no effect on any component of the perineural waveform, but promptly 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.